This question may seem tricky, but it is actually really simple. You need to read the question well; it states, ‘which would be the LEAST useful in managing the adverse event’ A is correct.

Blood donors should ensure they are well hydrated and have eaten well before donating blood. B is correct. Elevation of the legs would cause more blood to return to the heart and hence more blood to be pumped to the brain.

C is correct. People should not donate blood if their haemoglobin level is below the lower limit of normal.

E is correct. The donor should be encouraged to eat, rest and continue their normal activities as soon as possible after the donation.

This leaves us with D. If a donor faints whilst giving blood, YOU IMMEDIATELY STOP. You should never continue bleeding the donor if an adverse event has occurred or is about to occur.

She has signs and symptoms of anaemia. The blood picture shows pancytopenia which rules out pernicious anaemia as an underlying cause. Normal morphology rules out the possibility of acute myeloid leukaemia and acute lymphoblastic leukaemia.

From the age alone we can exclude chronic myeloid leukaemia as it usually presents at middle-age. A bone marrow aspirate that shows a gross reduction in all haemopoietic tissue that is replaced by fat spaces is seen classically in aplastic anaemia.

Absent reticulocytes support the diagnosis. Aplastic anaemia is a rare, potentially life-threatening failure of haemopoiesis characterised by pancytopenia and hypoplastic marrow (the marrow stops making cells).

Causes : Most cases are autoimmune, triggered by drugs (viruses, eg parvovirus,hepatitis) or irradiation.

Presentation : Aplastic anaemia can present abruptly over, or insidiously over, weeks to months. 

• Symptoms include pallor, headache, palpitations, dyspnoea,fatigue, or ankle oedema.

 Note: Anaemic symptoms are usually less severe due to the chronic onset.

• Symptoms of thrombocytopenia (skin or mucosal haemorrhage, visual disturbance due to retinal haemorrhage, petechial rashes.

• Infection (a less common presentation) particularly upper and lower respiratory tracts, skin, mouth, and peri-anal region.

• There is no lymphadenopathy or hepatosplenomegaly (in the absence of infection).

Diagnostic tests: Bone Marrow examination is needed for the confirmation of diagnosis.

Note: To define aplastic anaemia based on FBC and bone marrow findings, at least two of the following must be present:

• Haemoglobin <10 g/dL

• Platelet count < 50 x 109/L

• Neutrophil count <1.5 x 109/L

It is also important to note that the blood film morphology is unremarkable which differentiates it from some other types of leukaemias.

Acute lymphoblastic leukaemia (ALL) :

Most cases of acute leukaemia arise with no apparent cause. There are several well known associations with the development of acute leukaemia that are sometimes present. These include radiation exposure, chemotherapeutic agents, as well as some retroviruses.

Clinical Presentation : 

The most common presentation results from the effects of the leukaemic blast cells crowding out the normal marrow cells, resulting in symptoms of pancytopenia even if the total white blood cell count is normal.

• Fatigue from anaemia is the most common presenting complaint.

• Bleeding, petechiae, purpura or ecchymoses (due to thrombocytopenia)

• Recurrent and severe infections (oral, throat, skin, perianal infections commonly). This is because of the underproduction orabnormal function of white blood cells.

• Left upper quadrant fullness and early satiety due to splenomegaly(10-20%)

Acute lymphocytic leukaemia (ALL) is more common in children, and acute myeloid leukaemia (AML) is more common in adults, but they are in distinguishable clinically. This means you cannot determine the diagnosisonly from the clinical presentation. ALL is more often associated with infiltration of other organs, but AML can do it as well. Enlargement of the liver, spleen, and lymph nodes and bone pain are common at presentation.

Diagnosis : The FBC is the first clue to the diagnosis. Depression of all three cell lines is common at presentation.

• Anaemia is usual and Hb may be below 5 g/L 

• The white cell count can be low, normal, or elevated

• Thrombocytopenia

A bone marrow biopsy showing numerous blasts confirms the diagnosis of acute leukaemia. It is very unlikely that the questions would ask you to differentiate the AML from ALL using specific test. However, if a child (young age) is given with signs and symptoms of pancytopenia, ALL would be the most likely as it is the commonest childhood leukaemia.

The table below is a short summary of common findings given in the exam to help you differentiate between the cause of the anaemia.

Angular stomatitis, sore red tongue can ben seen in both B12 deficiency and iron deficiency although angular stomatitis is more of a sign of iron deficiency.

Koilonychia is usually seen in iron deficiency.

But the key to the question is the mean cell volume. As this is decreased, it cannot be B12 deficiency or folate deficiency. Iron deficiency leads to microcytic anaemia so we would expect the MCV to be low.

Iron-deficiency anaemia : Aetiology -

• Blood loss from the gastrointestinal (GI) tract is the most common cause of iron deficiency anaemia in adult men and post menopausal women

• Blood loss due to menorrhagia is the most common cause of irondeficiency in premenopausal women

• In tropical countries, infestation of the gut may cause iron deficiency anaemia, especially with hookworm and schistosomiasis

Laboratory tests :

• Low Haemoglobin

• Low Mean cell volume (MCV)

• Low Mean cell haemoglobin concentration (MCHC)

• High Red cell distribution width (RDW)

• Low serum ferritin

• High Total iron-binding capacity

The above laboratory test are important to remember.

This patient has an INR that is not within the therapeutic range and he has a major bleed.

For the purposes of the exam, a major bleed is an intracranial or a gastrointestinal haemorrhage and a minor bleed is haematuria or epistaxis.

If INR is higher than the target with a major bleed:

• Stop warfarin

• Give intravenous vitamin K 5 mg

• Prothrombin complex concentrate – if not available then give fresh frozen plasma

Anaemia in pregnancy as the following values Hb levels of: <11.0g/dl in the first trimester; <10.5 g/dl in the second and third trimesters <10.0 g/dl in the postpartum period.

Normal physiological changes in pregnancy

Haematological changes :

• Plasma volume increases over the course of pregnancy by about 50%. Dilutional anaemia is caused by the rise in plasma volume.

Elevated erythropoietin levels increase the total red cell mass by the end of the second trimester but haemoglobin concentrations never reach pre-pregnancy levels.

• Usually mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC) are unaffected.

• Serum iron falls during pregnancy whilst transferrin and total iron binding capacity rise. Many people get caught out with some of these physiological changes and class them as pathological whereas infact, they are completely normal in pregnancy.

Mediastinal masses are frequent and are sometimes discovered on a routine CXR in lymphoma. Tissue diagnosis is the best way to diagnose lymphoma. Lymph node excision biopsy is what is usually done.

The likely diagnosis here is the warm antibody induced haemolysis type of autoimmune haemolytic anaemia.

Most cases are idiopathic with no underlying pathology.

The low haemoglobin and high reticulocytes fit the picture.

Mild jaundice and spherocytes can also be seen.

Direct Coombs test is the investigation of choice.

Types :

1. Warm antibody type

2. Cold antibody type

Warfarin should always be stopped 5 days before planned surgery. Heparin is used instead of warfarin prior to surgery in patients with intermediate to high risk of thromboembolism, recent TIA or patients with mechanical cardiac valves.

Surgery and Warfarin If the person needs to have surgery or any other invasive procedure, they may need to temporarily stop taking warfarin.

The clinical picture here is one of multiple myeloma.

Multiple myeloma is a clonal abnormality of plasma cells. Bone pain that is at the back and ribs are common presentations.

Hypercalcaemia and an elevated ESR are features of multiple myeloma. Around 50% of patients with multiple myeloma would have renal impairment as seen in this stem by having an eGFR of 45. Bence-Jones is a protein not a cell.

MULTIPLE MYELOMA :

A clonal abnormality of plasma cells resulting in their overproduction replacing the bone marrow as well as the production of large quantities of functionless immunoglobulins.

Clinical Presentation :

• Bone pain is the most common clinical manifestation.

• This is most commonly in the back and the ribs, secondary to pathologic fractures.

• Recurrent bacterial infection

• Due to abnormal immunoglobulin production which are functionally impaired. Remember, although there are large quantities of immunoglobulins, they do not function well.

• Renal failure

• Anaemia may present with weakness, fatigue, and pallor.

• Hypercalcaemia may present with polyuria, polydipsia, and altered mental status. Rarely, symptoms of a hyperviscosity syndrome such as blurry vision, and confusion, may occur.

Diagnosis :

• Although a normochromic, normocytic anaemia is the most common laboratory finding, this is not specific for myeloma.

• A serum protein electrophoresis with a markedly elevated monoclonal immunoglobulin spike is present in almost all cases.

• Urine protein electrophoresis: looks for the presence of Bence Jones' protein.

• Plain x-ray of the skeletal system and skull will reveal the punched out lytic lesion caused by the overproduction of osteoclast activating factor from the plasma cells.

• Hypercalcaemia from the destruction of bone. Note that the hypercalcaemia is associated with normal alkaline phosphatase.

• Elevation in the BUN and creatinine from the damage to the kidney from the immunoglobulins.

• A bone marrow biopsy with abundance of plasma cells confirms a diagnosis of multiple myeloma.

• Rouleaux formation can be seen on blood film (rouleaux means a cylindrical packet of coins) 

This patient has a haemolytic anaemia.

A direct antiglobulin test is a synonym for a direct Coombs test. The direct Coombs test is used to test for autoimmune haemolytic anaemia or in other words any condition of an anaemia caused by immune system lysis or destruction of red blood cells.

The term “polychramasia” used in this stem refers to a disorder where there is an abnormally high amount of immature red blood cells. A haemolytic anaemia such as this case would trigger erythropoeitin release and increase the rate of which red blood cells are produced and released from the bone marrow. When levels of erythropoeitin are high, immature red cells would be released into the bloodstream.

COOMBS TEST : There are two Coombs tests:

1. The direct Coombs test 

2. The indirect Coombs test

Direct Coombs test :

• Used to test for autoimmune haemolytic anaemia

• It is used to detect these antibodies or complement proteins that are bound to the surface of red blood cells. Basically, it is used to test patients RED BLOOD CELLS.

• A positive Coombs test indicates that an immune mechanism is attacking the patient's own RBCs.

Indirect Coombs test :

• Used in prenatal testing of pregnant women and in testing blood prior to a blood transfusion.

• It detects antibodies against RBCs that are present unbound in the patient's serum.

In this case, serum is extracted from the blood sample taken from the patient and tested. Basically, it is used to test patients SERUM (not red blood cells). If agglutination occurs, the indirect Coombs test is positive.

Before looking at the cell types, think of the diagnosis.

The most likely diagnosis here is Acute lymphoblastic leukaemia (ALL) as he is young, suffering recurrent infections (due to abnormal WBCs), and having pale conjunctiva (anaemia). The bleeding gums and nose bleeds tell you that he has thrombocytopenia.

A very easy and direct question. The diagnostic cells in Hodgkin’s lymphoma are Reed Sternberg cells.

HODGKIN'S LYMPHOMA : Hodgkin's lymphoma is a malignant tumour of the lymphatic system that is characterised histologically by the presence of multi nucleated giant cells (Reed Sternberg cells). There are subtypes of Hodgkin's lymphoma but these are not commonly asked.

Presentation :

• Enlarged but otherwise asymptomatic lymph node, typically in the lower neck or supraclavicular region.

• The lymph nodes are described as painless, non-tender, and ‘rubbery’

• Mediastinal masses are sometimes discovered on a routine CXR.

• Systemic symptoms of drenching night sweats, unexplained fever >38°C, and weight loss of >10% over six months are termed B symptoms and are identified in approximately 25% of patients.

• Pruritus

• Lethargy

• Other findings include splenomegaly (30%) and hepatomegaly (10%)

• Superior vena cava syndrome may occur due to ta compresion from mediastinal lymph node

Diagnosis :

Lymph node excision biopsy.

Multiple myeloma is the suspected diagnosis here and needs to be dealt with by the haematologist. Elevation in the BUN and creatinine is seen due to the damage to the kidney from the immunoglobulins. Anaemia is the most common laboratory finding in multiple myeloma.

She is 90 years old. It is unlikely that her mother is still alive. The statement that she thinks her mother is going to visit her today points to some sort of confusion. This confusion can be seen in multiple myeloma due to hyperviscosity and also hypercalcaemia.

The signs and symptoms together with the normochromic, normocytic anaemia are indicative of multiple myeloma. Nose bleeds occur because the abnormal plasma cells found in multiple myeloma inhibit the production of platelets. Electrophoresis is already performed in this quesiton as monoclonal proteins can only be seen during electrophoresis.

Secondary care would arrange a bone marrow biopsy, skeletal survey and 24 hour urine collection before constructing a plan. Amongst the options of investigations, bone marrow biopsy would show an increased amount of plasma cells.

The condition that is described here is superficial thrombophlebitis.

NSAIDs have been shown to be effective in managing the pain for superficial thrombophlebitis. Thrombophilia is not required for investigation of patients with superficial thrombophlebitis. D-dimers would not be beneficial as it would usually be high after surgery. Furthermore, it would be raised in both superficial thrombophlebitis and deep vein thrombosis.

It is important in a patient who is deficient in both vitamin B12 and folic acid to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord. Once the vitamin B12 levels are normal, then start oral folic acid.

Most cases of haemolytic uremic syndrome develop in children after 2 to 14 days of diarrhoea often bloody, due to infection with a certain strain of E. coli. Common features include abdominal pain, fever, features of renal failure like vomiting can also occur.

Renal function and electrolytes would show a rise in urea and creatinine. This is due to dehydration but, if associated with haemolysis and thrombocytopenia, then it would indicate the onset of HUS.

Haemolytic uraemic syndrome (HUS): 

* HUS consists of a triad of haemolytic anaemia, uraemia, and thrombocytopenia.

* The anaemia will be intravascular in nature and will have an abnormal blood smear showing schistocytes, helmet cells, and fragmented red cells.

* LDH and reticulocyte count will be elevated and the haptoglobin decreased. 90% are caused by E. coli strain O157.

* This produces a verotoxin that attacks endothelial cells. Occurs after eating undercooked contaminated meat.

Signs and Symptoms: The classical presenting feature is profuse diarrhoea that turns bloody 1 to 3 days later.

Management :

• Treatment is supportive e.g. Fluids, blood transfusion and dialysis if required

• Do not give antibiotics to those with possible HUS. The organism may release more toxins as it dies if antibiotics are given and may worsen the disease.

• The indications for plasma exchange in HUS are complicated.

For major bleedings, these are the necessary steps:

• Stop warfarin

• Give intravenous vitamin K 5 mg

• Prothrombin complex concentrate – if not available then give fresh frozen plasma

The signs and symptoms point towards a beta thalassaemia major. Alpha thalassemia trait have mild anaemia and are usually clinically asymptomatic Thalassaemias.

Thalassaemia major - Is usually lethal in utero. It should be considered when hydrops fetalis is diagnosed.

Thalassaemia major - Presents in infancy often includes failure to thrive, vomiting feeds, sleepiness, stunted growth and irritability. In severe, untreated cases there may be -

• Hepatosplenomegaly

• Bony deformities (frontal bossing). 

• Marked pallor and slight to moderate jaundice

• Iron overload can cause endocrinopathy with diabetes, thyroid, adrenal and pituitary disorders

* Thalassaemia carrier status is often confused with iron deficiency due to reduced MCV and MCH.

But note that in iron deficiency, serum ferritin and iron is low while in thalassaemia they are usually high.

Management for thalassaemia major:

• Lifelong blood transfusions are needed to maintain a haemoglobin level higher than 9.5 g/dL.

• Iron chelation to prevent overload syndrome (Oral deferiprone + desferrioxamine SC twice weekly)

Anaemia, raised WBC count are known features of chronic myeloid leukaemia (CML).

Splenomegaly is very suggestive of chronic myeloid leukaemia (CML) and Philadelphia chromosome is diagnostic of chronic myeloid leukaemia (CML).

Haemophilia A and B

• Are congenital bleeding disorders with low levels of factor VIII (haemophilia A) or IX (haemophilia B, Christmas disease).

• Sex-linked inheritance.

• Males are typically affected

• Female carriers are rarely symptomatic

* Spontaneous haemarthrosis are virtually pathognomonic.

Investigations :

• Prothrombin time, bleeding time, fibrinogen levels are normal

• Activated partial thromboplastin time (APTT) is usually prolonged 

• In Von willebrand disease, aPTT and bleeding time are prolonged.

Disseminated intravascular coagulation (DIC) :

• Ecchymoses or spontaneous bleeding at venepuncture sites, and the site of trauma

• Bleeding from ears, nose and throat, gastrointestinal tract

• Petechiae, purpura

Diagnosis : No single laboratory test that can establish or rule out the diagnosis of DIC, therefore assess the whole clinical picture, taking into account the clinical condition of the patient, and all available laboratory results.

• Thrombocytopenia around 50% of them would have a platelets count less than 50 x 109/L

• D-dimer is elevated

• Prothrombin time (PT) is elevated

• Activated partial thromboplastin time (aPTT) is elevated

• Fibrinogen level low

Remember, everything is elevated except platelets and fibrinogen.

Treatment  :

• Treat the underlying condition

• Transfusion of platelets or plasma (components) for patients with severe bleeds

• In bleeding patients with DIC and prolonged PT and aPTT, administer fresh frozen plasma (FFP)

Angular stomatitis is a known sign for iron deficiency anaemia however vitamin B12 deficiency is sometimes responsible for angular stomatitis, and commonly occurs together with folate deficiency.

The appearance of the tongue in vitamin B12 deficiency is described as "beefy" or "fiery red and sore". Peripheral paresthesia is also a known symptom of vitamin B12. Vitamin B12 deficiency has RBC changes which include oval macrocytosis.

The clincher here is the massive spleen. Although there are many causes of massive spleen, massive spleen can only be caused by chronic myeloid leukaemia (CML) or Malaria. Weight loss, lethargy, increasing abdominal discomfort support the diagnosis of CML.

If you see a middle aged man/woman with a huge spleen it is likely to be Chronic myeloid leukaemia (CML). Malaria would likely have a travel history of some sort.

Mnemonic: CML (Crazy Massive Large Spleen)

A bone marrow biopsy with abundance of plasma cells is diagnostic for multiple myeloma.

All the indications point toward this patient having a haemolytic anaemia. A direct antiglobin test is a synonym for a direct Coombs test which would be appropriate to test for autoimmune haemolytic anaemia. Haemolysis causes an increase in the serum bilirubin levels, which is present in this patient’s blood results.

The only blood values that are not within the normal range for this patient are her haemoglobin levels, her MCV value and her bilirubin levels. Everything else is within the normal range.

What about the increased MCV?

While it is true that most cases of an increased mean cell volume can be seen in the macrocytic anaemias notably B12 deficiency and folate deficiency which are, by definition, not haemolytic anaemias, some immunologically-mediated haemolytic anaemias may be seen to have spherocytes on microscopy and have an increased MCV. These immunologically-mediated haemolytic anaemias would have a positive direct Coombs test.

The evidence of increased MCHC, gallstones and family history points towards hereditary spherocytosis.

Anaemia, raised WBC count are known features of chronic myeloid leukaemia (CML). Myeloid cells include neutrophils, basophils, eosinophils, erythrocytes, and platelets. An increased number of neutrophils, basophils, eosinophils are consistent with CML. Note that platelets can be low, normal or raised in CML.

Rash over buttock, abdominal pain and vomiting, blood in urine or stool suggest Henoch-Schönlein purpura. A mixed picture question like this can be sometimes confusing as in this question there are some features of a non accidental injury (stepfather). Be sure to evaluate all the signs and symptoms before jumping to the conclusion that this is a non accidental injury.

Henoch-Schönlein purpura (HSP) :

• Purpura (non-blanching) over buttocks and extensor surfaces

• Arthralgia (especially in the knees and ankles)

• Abdominal pain

Diagnosis:

• Mainly a clinical diagnosis

• Look for elevated ESR, IgA

• Raised creatinine ; labs consistent with nephropathy

Treatment:

• Self-limiting; conservative management

• NSAIDs for arthralgic pain; beware of choosing this option if case stem has impaired renal involvement!

• Corticosteroids can improve associated arthralgia and the symptoms associated with gastrointestinal dysfunction.

Factor IX deficiency is evidence of haemophilia B (Christmas disease)

Heinz bodies are pathognomic for G6PD deficiency. In exam, if you see a question that has Heinz bodies on a blood film, you can almost be certain that this is G6PD deficiency.

Haemolysis in this case was elicited by treatment of malaria. Usually primaquine is the culprit.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is X-linked and clinically important cause of oxidant haemolysis.

It has recently been established that a mutation in JAK2 is present in approximately 95% of patients with PRV. JAK2 mutation is now a major criteria in the diagnosis of polycythaemia rubra vera.

Polycythaemia rubra vera (PRV) is the most common form of primary polycythaemia.

It is a malignant proliferation of a clone derived from one pluripotent marrow stem cell.

• There is excess proliferation of RBCs, WBCs, and platelets, leading to hyperviscosity and thrombosis

• More commonly found in patients who are more than 60 years old

• A mutation in JAK2 is present in >90%

Presentation :

• It may be discovered on routine blood count in a person with no related symptoms or there may be nonspecific complaints of lethargy and tiredness

• About a third present with symptoms due to thrombosis. Features include stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism

• Headaches, dizziness, sweating, and tinnitus

• Bleeding from gums or easy bruising is usually mild but gastrointestinal haemorrhage can be more severe. This is secondary to abnormal platelet function.

• Pruritus which is typically worse after a hot shower or bath

• Splenomegaly is present in about 75% of patients.

• Hypertension is common

• Erythema, warmth, pain, and even sometimes infarction of the distal extremities. Burning sensation in fingers and toes, are characteristic but not very common.

• Facial plethora

• Gout from increased cell turnover

Management : Venesection

There are two major points mentioned here: cervical lymphadenopathy and splenomegaly. This combination makes Non-Hodgkin lymphoma as the most likely cause.

Toxoplasmosis although uncommon, may have cervical lymphadenopathy and splenomegaly as well. But weight loss is not seen in toxoplasmosis hence nonhodgkin's lymphoma remains the top choice.

Haemolysis in this case was elicited by the treatment of malaria using primaquine. This patient has G6PD deficiency.

The signs and symptoms are consistent with polycythaemia rubra vera (PRV) About a third of patients with PRV present with symptoms due to thrombosis. This includes DVT like in this question. PCV is usually associated with a low serum level of the hormone erythropoietin.

The 3 important points you need to know in Von Willebrand disease :

1. It presents with mucosal bleeding, Epistaxis, menorrhagia

2. Autosomal dominant (type 3 is recessive)

3. Role of Von Willebrand's factor is: a. Promotes platelet aggregation b. Carrier molecule for factor VIII

Investigation

• Bleeding time prolonged

• APTT prolonged

• Factor VIII levels may be moderately reduced

Management :

• Tranexamic acid for mild bleeding

• Desmopressin

• Factor VIII concentrate

As a general rule, platelet deficiency causes petechial haemorrhages and ecchymoses (bruising) whilst clotting factor deficiency produces haematomas and haemarthroses.

This question gives a mixed picture where there are descriptions of both platelet deficiency (petechial haemorrhages seen on his buttocks) and factor deficiency (bleeding/swelling at his knee). However, the prolonged aPTT supports the diagnosis of haemophilia thus that is the answer. 

This is a frequently asked topic. Be sure to know the differentiations between all the leukaemias and be able to classify them by the age groups.

Acute lymphoblastic leukaemia (ALL) is the most common paediatric cancer.

The differentiating factor between ALL and acute myeloid leukaemia (AML) is AML would present with massive splenomegaly on examination. ALL would just have lymphadenopathy.

Acute lymphocytic leukaemia (ALL) is more common in children, and acute myelogenous leukaemia (AML) is more common in adults. However, if a child (young age) is given with signs and symptoms of pancytopenia, ALL would be the most likely as it is the commonest childhood leukaemia.

This elderly man is probably quite aggressive and difficult to manage. The presence of bruising on the forearms is reflective of him trying to defend himself and push someone away. The facial bruising is suspicious of abuse.

Option B. Accidental falls is incorrect. Most injuries in these cases involve hip joints or shoulder joints. There is no mention of hip or shoulder pains in this case.

Option C. Heparin induced thrombocytopaenia is incorrect. There is no history of use of heparin Option D.

The blood results are all normal. The rash in the legs that are non blanching and the arthritis are hints towards Henoch-Schönlein purpura.

The disease occurs mostly in the winter months. About 50-90% of patients have a preceding upper respiratory tract infection (URTI) which explains the cough in the given question. The stem here gives no history of fever.

Generally, patients with Henoch-Schönlein purpura appear to be mildly ill, with low-grade fever. But having no fever does not exclude the diagnosis.

Heinz bodies are pathognomic for G6PD deficiency. In exam, if you see a question that has Heinz bodies on a blood film, you can almost be certain that this is G6PD deficiency.

The commonest leukaemia in children is Acute lymphoblastic leukaemia (ALL).

Bleeding gums (low platelet), feeling tired and lethargic, sore throat, splenomegaly are all well known features of Acute lymphoblastic leukaemia (ALL)

Haemolysis in G6PD deficiency patients can be elicited by treatment of malaria. Back pain and abdominal pain can be seen in severe haemolysis occurring in G6PD deficiency. History of gallstones and neonatal jaundice support the diagnosis of G6PD deficiency.

All his blood results are normal. Anatomical defect is the only possiblity.

The purpuric rash found in HSP is typically over buttocks and extensor surfaces of arms and legs. Arthrlagia occurs in 80% of patients and gastrointestinal symptoms like abdominal pain occur in around 30% of patients. Renal involvement is usually seen in the older children which can be identified by microscopic haematuria or proteinuria.

Parvovirus B19 infection can cause an aplastic crises in patients with hereditary spherocytosis. This can be life-threatening and often requires blood transfusion. Splenic sequestration crisis is a wrong answer. A patient with a sequestration crisis is also severely anaemic , but the reticulocyte count will be high, in contrast to the aplastic crisis where the reticulocyte count is low or zero. Splenic sequestration crisis is also usually seen in sickle cell.

The best option above is folate deficiency as it is a macrocytic anaemia (high MCV)

This is quite the classical presentation of lymphoma.

• Drenching night sweats, fever, weight loss

• Enlarged but otherwise asymptomatic lymph node, typically in the lower neck or supraclavicular region

• Occasionally, findings on examination may reveal hepatomegaly or splenomegaly.

The signs and symptoms are consistent with polycythaemia rubra vera (PRV). Gout can be seen in PRV. This is due to an increased cell turnover.

The clincher here is the massive spleen that approaches the right iliac fossa. Although there are many causes of massive spleen, for the purpose of exam, massive spleen can only be caused by chronic myeloid leukaemia (CML) or malaria.

If you see a middle aged man/woman with a huge spleen likely to be Chronic myeloid leukaemia (CML). Malaria would likely have a travel history of some sort. 

Anaemia, raised WBC count are known features of chronic myeloid leukaemia (CML).

Splenomegaly (particularly if massive) is very suggestive of chronic myeloid leukaemia (CML) and Philadelphia chromosome is diagnostic of chronic myeloid leukaemia (CML). Note that platelets can be normal in CML.

Factor VIII deficiency is evidence of haemophilia A. Desmopressin is one of the treatment choices.

This is actually an acute emergency. The leucocytosis is causing the bone pain. Bleeding from the gum is commonly seen in acute myeloid leukaemia (AML).

Note that gum bleeding can also be seen in ALL. AML is the most common acute leukaemia in adults.

Thus, majority of the acute leukaemia in children questions asked in the exam would be acute lymphoblastic leukaemia (ALL) and not acute myeloid leukaemia (AML). One needs to be careful with picking AML or ALL as there are often questions with a very similar stem.

In reality, it is difficult to diagnose them clinically as well. Flow cytometry (immunophenotyping) is used to help distinguish AML from acute lymphocytic leukemia (ALL).

• Bone marrow aspiration is the diagnostic procedure. 

Idiopathic thrombocytopenic purpura is usually seen in children but that does not mean it can’t happen in adults. Chronic ITP which is mainly seen in women can run a fluctuating course of bleeding, purpura, epistaxis and menorrhagia. The isolated thrombocytopenia in a well patient points to a diagnosis of idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura in adults. unlike ITP in children, adult ITP does not normally follow an infection and usually has an insidious onset. It is more likely to follow a chronic course in affected adults than in children.

Presentation:

• As in children, adults with ITP may demonstrate a range of symptoms from none at all through to severe haemorrhage

• Bleeding, purpura, epistaxis and menorrhagia

Laboratory diagnosis :

• Isolated thrombocytopenia; blood count otherwise normal

Management:

• Prednisolone

• IV immunoglobulin

• Emergency platelet transfusion - Only in life threatening haemorrhage. 

G6PD enzyme activity is the definitive test Osmotic fragility test is to diagnose Hereditary spherocytosis. Heinz bodies and bite cells seen on blood film are important investigations that point towards G6PD but are not the definitive diagnostic test.

The blood values are indicative of a microcytic anaemia. It is true that methotrexate can cause a folic acid deficiency anaemia but since the blood results clearly show a microcytic anaemia (and folic acid deficiency anaemia is a macrocytic anaemia) the only correct conclusion that we can reach is that the long term NSAID therapy is the culprit for her anaemia.

Idiopathic thrombocytopenic purpura is usually seen in children but that does not mean it can’t happen in adults.

As the patient is otherwise well, acute leukaemia, HIV and SLE are unlikely. A normal WBC count excludes aplastic anaemia. Thus the likely diagnosis is ITP.

Idiopathic thrombocytopenic purpura fits with her symptoms of bruising and petechiae. Older girls may have menorrhagia. Some experience nose bleeds. The isolated thrombocytopenia in a well patient points to a diagnosis of idiopathic thrombocytopenic purpura.

The INR range of 2 to 3 is appropriate for:

• Prophylaxis or treatment of venous thromboembolism

• Reduction of the risk of systemic embolism for people with atrial fibrillation and valvular heart disease.

For the purpose of exam, just remember that INR of 2 to 3 is the answer for majority of cases.

The only cases where a higher INR is required, is in the cases of a mechanical heart valve replacement. Patients with metallic valves require lifelong anticoagulation with a target INR of 3 to 4.

Anaemia, raised WBC count, low platelet (platelet may be variable) are known features of Chronic myeloid leukaemia (CML).

Splenomegaly is very suggestive of Chronic myeloid leukaemia (CML) and Philadelphia chromosome is diagnostic of Chronic myeloid leukaemia (CML).

Although both Hodgkin’s and Non-Hodgkin’s lymphoma present in similar ways with lymphadenopathy, night sweats, fever, weight loss, non-Hodgkin’s is more associated with HIV than hodgkin’s disease. Non-Hodgkin's lymphoma (NHL) is known as AIDS related lymphoma.

The most prevalent of the HIV-related lymphomas is diffuse large B-cell non-Hodgkin's lymphoma, followed by Burkitt's lymphoma.

Methotrexate is a folate antagonist. It causes folate deficiency which is shown as a macrocytic anaemia like in the case above. Anaemia of chronic disease would be considered as a cause if the MCV was normal or low. Rheumatoid arthritis leading to anaemia of chronic disease has red cells that are usually hypochromic, microcytic or normochromic, normocytic.

According to her lab results, this woman appears to have a pancytopenia (reduction in all three haematopoietic cell lines). In order to prove a diagnosis of aplastic anaemia, a bone marrow biopsy must be done. Please note that pancytopenia and aplastic anaemia are NOT interchangeable terms.

• Pancytopenia is a decrease in all three haematopoietic cell lines. Pancytopenia can be suspected from a full blood count with or without a peripheral blood smear.

• Aplastic anaemia is pancytopenia AND histological evidence of a hypoplastic bone marrow. It is a diagnosis of exclusion and can only be made by a bone marrow biopsy.

She has signs and symptoms of anaemia. The blood picture shows pancytopenia which rules out pernicious anaemia as an underlying cause. Normal morphology rules out the possibility of acute myeloid leukaemia, and acute lymphoblastic leukaemia.

Chronic myeloid leukaemia usually has leucocytosis. A bone marrow aspirate that shows a gross reduction in all haemopoietic tissue is seen classically in aplastic anaemia. Decrease reticulocytes support the diagnosis.

This is a multi-part question. Her symptoms are indicative of hypothyroidism. Her signs are indicative of Hashimoto’s Thyroiditis (an autoimmune thyroid disorder).

Since Hashimoto’s is an autoimmune disease and her blood smear shows a macrocytic anaemia, a logical conclusion would be that she is suffering from pernicious anaemia (also an autoimmune disease).

When you see parvovirus B19 in the exam, immediately think of sickle cell anaemia or hereditary spherocytosis with the diagnosis of aplastic crisis at hand. Parvovirus is also a risk factor for splenic sequestration crisis however infection with parvovirus B19 is more commonly associated with aplastic crisis in patients with sickle cell anaemia.

In adults, parvovirus B19 can present with flu-like symptoms and symmetrical joint pain and stiffness involving joints of the hands, knees, wrists and ankles. This usually resolves in weeks. Another group of people that you should be worried about parvovirus infections are pregnant women as they can affect the fetal red blood cells causing aplastic anaemia. The anaemia can be particularly severe due to the short life span of fetal erythrocytes.

The mean cell volume is increased. This points towards either a B12 deficiency or folate deficiency. Pernicious anaemia is one of the causes of a B12 deficiency and it may coexist with other autoimmune disease such as vitiligo. Note that hypothyroidism is also another coexisting autoimmune disease to look out for.

Activated partial thromboplastin time (APTT) that is prolonged with everything else being normal points towards haemophilia. Factor VIII and IX levels should be offered to confirm the diagnosis.

The isolated thrombocytopenia and history of an upper respiratory tract infection with the development of purpura suggest idiopathic thrombocytopenic purpura. In idiopathic thrombocytopenic purpura, bleeding time may be increased like the above.

Idiopathic thrombocytopenic purpura :

• Follows viral infection or immunisation

• The most common presentation is petechiae or bruising. Petechiae mainly in arms and legs - sudden onset

• Up to a quarter present with nosebleeds

• Haematuria and gastrointestinal bleeds are less common.

• Older girls may have menorrhagia

• Otherwise the patient is well and physical examination is normal

Laboratory diagnosis :

• Isolated thrombocytopenia; blood count otherwise normal

Management:

• Prednisolone

• IV immunoglobulin

• Emergency platelet transfusion

• Only in life threatening haemorrhage.

The diagnosis here is Chronic lymphocytic leukaemia (CLL) which has mature lymphocytes on the blood film. Factors that support the diagnosis of CLL in this question:

• His age (75 years old) - In the exam, if you see an elderly patient (usually more than 65 years old) with symptoms of leukaemia, it is most likely CLL. However, read the whole question before you make a decision on the answer.

• Cervical lymphadenopathy

• Recurrent infections - dysfunctional WBC

• Pale conjunctiva  Anaemia On blood film, B cell lymphocytosis will be seen often with smudge cells.

There are some precipitating factors of haemolysis causing jaundice in patients with G6PD deficiency. Among then include infection. Bite cells point towards the diagnosis of G6PD.

This patient has a vitamin B12 deficiency due to low intake. Vegan diet patients such in the above stem is already a huge hint towards vitamin B12 deficiency. The fact that he has a low BMI is a hint that he has an improper diet.

The signs and symptoms are nonspecific – you cannot clinically differentiate between B12 deficiency anaemia and folic acid deficiency but for exam remember that patients with B12 deficiency often present with some form of neurological disturbance (peripheral neuropathy in this stem).

As there is no option for hydroxycobalamin alone, pick the one with the combination of hydroxycobalamin and folic acid.

Blood transfusion should NOT be considered if the patient has no symptoms of anaemia where the Hb is 80 g/L or more.

This patient is suffering from tumour lysis syndrome.

Tumour lysis syndrome is a severe metabolic disturbance following the rapid lysis of malignant cells a short while after chemotherapy, radiotherapy, surgery or ablation procedures. It is an oncological emergency.

It occurs most often in patients with acute lymphoblastic leukaemia (ALL) or Burkitt’s lymphoma.

In this stem, Burkitt’s lymphoma was present. Tumour lysis syndrome would result in the following blood results -

• Hyperuricaemia

• Hyperkalaemia

• Hyperphosphataemia

• Hypocalcaemia

Although a full biochemical profile is needed to diagnose tumour lysis syndrome uric acid levels would help confirm the diagnosis of tumour lysis syndrome.

TUMOUR LYSIS SYNDROME :

• History of Leukaemia or Burkitt’s lymphoma

• Chemotherapy

• Acute renal failure

• Hyperuricaemia, hyperkalaemia, hyperphosphataemia, hypocalcaemia

• IV fluids as part of management

The prolonged aPTT supports the diagnosis of haemophilia. Between both haemophilia A and B, haemophilia A is more common and it accounts for 90% of cases of haemophilia.

Gastrointestinal haemorrhage would be a cause of microcytic anaemia like in the given scenario and it fits with the history of prolonged use of NSAIDS. Folate and B12 deficiency are in the category of macrocytic anaemias. There should be no reason for menorrhagia. Besides, the patient is 52 years old. The average age of menopause is 51. Blood loss from the gastrointestinal (GI) tract is the most common cause of iron deficiency anaemia in postmenopausal women. There is also no relation with haemorrhoids.

Acute abdominal pain may indicate concealed abruptio placentae which may be a cause of disseminated intravascular coagulation.

The two top choices here are HELLP syndrome and disseminated intravascular coagulation (DIC). It is important to understand that HELLP syndrome may lead to disseminated intravascular coagulation.

But the more specific answer in this question is DIC because in HELLP syndrome, the prothrombin time, activated partial thromboplastin time and serum fibrinogen levels are normal but are prolonged in DIC. Bilirubin levels may be higher than normal due to bilirubin production secondary to haemolysis.

The signs and symptoms are consistent with polycythaemia rubra vera (PRV) Hypertension is found in 30% of patients with PRV. Splenomegaly is found in 75% of patients at the time of diagnosis.

The mass in the left upper quadrant represents the spleen (splenomegaly) Burning sensation in fingers and toes, are characteristic.

PCV is usually associated with a low serum level of the hormone erythropoietin (EPO). However, everything else in this question points towards PRV.

Despite the fact that many people remember haemophilia presenting with bleeding into joints and muscles, you would need to know that epistaxis may occur in haemophilia. Activated partial thromboplastin time (APTT) that is prolonged with everything else being normal points towards haemophilia. Factor VIII and IX levels should be offered to confirm the diagnosis.

The patient has microcytic anaemia which can fit with the diagnosis of anaemia of chronic disease. In anaemia of chronic disease, red cells are often normochromic, normocytic, but may be hypochromic, microcytic (as frequently seen in rheumatoid arthritis and Crohn's disease)

Folate and B12 deficiency are in the category of macrocytic anaemias. There should be no reason for menorrhagia. Besides, the patient is 53 years old. There is also no relation with haemorrhoids.

Disseminated intravascular coagulation (DIC) :

* Ecchymoses or spontaneous bleeding at venepuncture sites, and the site of trauma

* Bleeding from ears, nose and throat, gastrointestinal tract

* Petechiae, purpura

Diagnosis : No single laboratory test that can establish or rule out the diagnosis of DIC, therefore assess the whole clinical picture, taking into account the clinical condition of the patient, and all available laboratory results.

* Thrombocytopenia around 50% of them would have a platelets count less than 50 x 109/L

• D-dimer is elevated

• Prothrombin time (PT) is elevated

• Activated partial thromboplastin time (aPTT) is elevated

• Fibrinogen level low

Remember, everything is elevated except platelets and fibrinogen.

Treatment :

• Treat the underlying condition

• Transfusion of platelets or plasma (components) for patients with severe bleeds

• In bleeding patients with DIC and prolonged PT and aPTT, administer fresh frozen plasma (FFP)

The white, vertical lesion described is called hairy leukoplakia which occurs primarily in HIV-positive individuals. Hairy leukoplakia is a condition that is characterised by irregular white patches on the side of the tongue and occasionally elsewhere on the tongue or in the mouth.

It is a form of leukoplakia, which refers to white patches on the mucous membranes of the mouth often arising in response to chronic irritation. Hairy leukoplakia occurs primarily in HIV-positive individuals. This white lesion cannot be scraped off. The lesion itself is benign and does not require any treatment.

Acute lymphoblastic leukaemia (ALL) :

Clinical Presentation : The most common presentation results from the effects of the leukaemicblast cells crowding out the normal marrow cells, resulting in symptoms of pancytopenia even if the total white blood cell count is normal.

• Fatigue from anaemia is the most common presenting complaint.

• Bleeding, petechiae, purpura or ecchymoses (due to thrombocytopenia)

• Recurrent and severe infections (oral, throat, skin, perianalinfections commonly). This is because of the under production or abnormal function of white blood cells.

.• Left upper quadrant fullness and early satiety due to splenomegaly.

Diagnosis : The FBC is the first clue to the diagnosis.

Depression of all three cell lines is common at presentation.

The two main contenders for an answer to this question are tuberculosis and lymphoma. Tuberculosis is improbable because New York City (USA) is not a tuberculosis prone area. The main TB prone areas that you have to take note of for your exam is a patient travelling to or from South Asia or sub-Saharan Africa.

While it is true that the signs and symptoms of tuberculosis and lymphoma are very similar the following table makes is easy to differentiate between tuberculosis and lymphoma if you are having difficulty choosing either as an answer.

Iron-deficiency anaemia :

• Blood loss from the gastrointestinal (GI) tract is the most common cause of iron- deficiency anaemia in adult men and postmenopausal women

• Blood loss due to menorrhagia is the most common cause of iron deficiency in premenopausal women

• In tropical countries, infestation of the gut may cause irondeficiency anaemia , especially with hookworm and schistosomiasis

Laboratory tests :

• Low Haemoglobin

• Low Mean cell volume (MCV)

• Low Mean cell haemoglobin concentration (MCHC)

• High Red cell distribution width (RDW)

• Low serum ferritin

• High Total iron-binding capacity.

The age is the only factor that support the diagnosis of acute lymphoblastic leukaemia (ALL) along with the given picture. The same picture can happen in aplastic anaemia but there is not a single factor mentioned in favour of it. So acute lymphoblastic leukaemia (ALL) can be taken as best option in the given scenario.

This woman has an isolated decrease in platelets with no other complaints (other than menorrhagia). The presence of petechiae is an additional clue to thrombocytopaenia.

Venesection is the most appropriate. Splenectomy is something to consider in the management of PCV. But it is usually down the line when there is painful splenomegaly or there are repeated episodes of splenic infarction.

Spherocytes are usually seen in hereditary spherocytosis and autoimmune haemolytic anaemias. However, they may be seen in G6PD deficiency as well in severe haemolysis. The history of consumption of fava beans followed by rapid deterioration points towards G6PD deficiency. Otherwise, in the exam, if you see spherocytes, it is almost always either hereditary spherocytosis or autoimmune haemolytic anaemias.

One calf having a larger diameter than the other is one one of the known signs of a DVT. The risk factors (smoker, immobile, major surgery) that are given also point clearly towards the likely diagnosis of deep vein thrombosis.

There are two major points mentioned here: cervical lymphadenopathy and splenomegaly.

This combination makes Non-Hodgkin lymphoma as the most likely cause Toxoplasmosis although uncommon, may have cervical lymphadenopathy and splenomegaly as well. But weight loss is not seen in toxoplasmosis hence non hodgkin's lymphoma remains the top choice.

An indirect Coombs test would test patient’s serum rather than red blood cells. This is appropriate as we would like to identify antigenicity. By doing the indirect Coombs test we are able to detect antibodies against RBC that are present unabound in the patient’s serum.

The signs and symptoms along with the hypercalcaemia point towards multiple myeloma. Breathlessness occurs due to anaemia found in multiple myeloma. Rouleaux formation can be seen on the blood film in multiple myeloma.

This stem shows a diagnosis of secondary polycythaemia due to chronic hypoxia. Patients who are long term smokers who have an underlying chronic obstructive pulmonary disease may have polycythaemia as a complication.

The long term hypoxia triggers an increased production of erythropoietin by the kidneys so that it stimulates the bone marrow cells to produce more red blood cells to transport oxygen to tissue.

Patients can present with non-specific symptoms such as lethargy, tiredness and headaches.

Other important causes of secondary polycythaemia due to hypoxia include :

• High altitudes

• Cyanotic congenital heart disease

The blood results are all normal. The rash in the legs that are non blanching and the arthritis are hints towards Henoch-Schönlein purpura.

The disease occurs mostly in the winter months. About 50-90% of patients have a preceding upper respiratory tract infection (URTI) which explains the cough in the given question. The stem here gives a no history of fever. Generally, patients with Henoch-Schönlein purpura appear to be mildly ill, with low-grade fever. But having no fever does not exclude the diagnosis.

Secondary polycythaemia (more accurately secondary erythrocytosis) is the answer. Erythrocytosis has many causes which include primary (polycythaemia rubra vera) or secondary (living at high altitudes, smokers, patients with COPD). The fact that platelets and white cell counts are within the normal range suggest a secondary cause rather than polycythaemia rubra vera.

Chronic smokers are at risk of developing secondary erythrocytosis due to chronic hypoxemia which triggers increased production of erythropoietin by the kidneys. If repeated haemoglobin is still high in 2 months time, further investigations would be warranted.

This patient has an INR between 6 and 8 without bleeding. He needs his warfarin stopped until his INR to repeat it the following day.

This lump is concerning and with the systemic symptoms of night sweats, fever and weight loss are termed B symptoms. Hodgkin’s lymphoma can occur in the paediatric population (usually older children). Splenomegaly is seen in 30% of all cases of Hodgkin’s lymphoma.

“B” symptoms :

• Weight loss of more than 10% of body weight during the previous 6 months

• Unexplained fever

• Drenching night sweats

Another take home point from this question is that Hodgkin’s lymphoma has a bimodal age distribution. It has two incident peaks. One peak around age 20 to 29 years of age and another at 60 years of age.

Chronic lymphocytic leukemia is a type of cancer in which the bone marrow makes too many lymphocytes that look mature but with defective functions.

The age of the patient is usually above 50 years. There is lymphadenopathy and splenomegaly. Repeated chest infection points towards abnormal function of lymphocytes against infection.

This is a blood and bone marrow disease that usually gets worse slowly. Therefore survival rates for chronic lymphocytic leukemia are good compared to many other cancers.

Chronic lymphocytic leukemia is a type of cancer in which the bone marrow makes too many lymphocytes that look mature but with defective function. The age of the patient is usually above 50 years.

There is lymphadenopathy and splenomegaly.

Recurrent infections point towards abnormal function of lymphocytes against infection. Pale conjunctiva is due to anaemia. This is a blood and bone marrow disease that usually gets worse slowly. Therefore survival rates for chronic lymphocytic leukemia are good compared to many other cancers.

This is macrocytic anaemia. The cause here is vitamin B12 or folate deficiency.

Points in favour of Vit. B12 or folate deficiency:

i) Fatigue (anaemia)

ii) Angular stomatitis (can be seen in Vit. B12 or folate deficiency)

iii) Absence of koilonychea is against IDA (Iron Deficiency Anaemia)

Diagnosis is chronic myeloid leukemia. An increased number of matured granulocytes and huge splenomegaly are diagnostic features of CML.

The following points favours the diagnosis of ALL :

i) Age- 6yrs

ii) recurrent infection (sore throat) due to neutropenia and abnormal lymphoblasts which cannot protect from infection

iii) thrombocytopenia causing gum and nose bleeding.

iii) anaemia (pale conjunctiva) due to reduced red cell production from marrow occupation by blast cells.

It cannot be confirmed unless we do bone marrow aspiration.

Normally ALL CBC shows raised WBC, low RBC, and low platelet; but it is also possible for all cell lines to be depressed, as is the presented case.

Vitamin B12 cannot be absorbed without intrinsic factor.

Vit B12 is absorbed mostly in the ileum. As ileal resection is done B12 is not absorbed leading to megaloblastic anaemia.

Points in favour of CML :

i) Age 57 years

ii) Weight loss

iii) Abdominal discomfort

iv) Anaemia

v) Fever

vi) Marked splenomegaly and high WBC count.

Polycythemia vera.

Points in favour are :

i) Hyperviscosity symptoms (headache, dizziness, tinnitus, visual problem)

ii) Pruritus, typically after a hot bath

iii) Splenomegaly

iv) RBC 87, Hb 31.9, Plt 796

Intrinsic factor deficiency affects oral B12 utilization.

Points in favour of CML :

i) Weight loss

ii) Lethargy

iii) Abdominal discomfort

iv) Splenomegaly

v) Gout (Elevated uric acid and vitamin B12 levels are found in 25% of patients of CML).

A blood picture is suggestive and +ve Philadelphia chromosome is diagnostic.

As the patient is otherwise well acute leukemia, HIV, and SLE are unlikely. Normal WBC count excludes aplastic anemia. So likely diagnosis is ITP. Isolated thrombocytopenia with bruising and petechiae and menorrhagia are strong indicators of ITP.

Idiopathic thrombocytopenic purpura is a type of thrombocytopenic purpura defined as an isolated low platelet count with normal bone marrow in the absence of other causes of low platelets.

Two distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults.

The acute form often follows an infection and spontaneously resolves within two months. Chronic immune thrombocytopenia persists longer than six months with a specific cause being unknown.

ITP is an autoimmune disease with antibodies detectable against several platelet surface structures and the immune system destroys these antibody-bearing platelets.

It may be graves disease with pernicious anemia. Lemon-yellow pallor occurs in pernicious anemia. Both are autoimmune diseases which favours this association. Hyperthyroidism may cause persistently raised body temperature, weight loss, and diarrhea.

In pernicious anemia there is a lack of intrinsic factors which is needed to absorb vitamin B12 and as this vitamin is not absorbed in pernicious anemia there occurs macrocytic anemia that leads to high MCV.

The commonest leukemia in children is ALL. Bleeding gums (low platelet), feeling tired and lethargic, sore throat, and hepatosplenomegaly all are well-known features of ALL.

Acute lymphoblastic leukaemia (ALL) is a type of blood cancer that starts from young white blood cells called lymphocytes in the bone marrow. Adults and children can get it but it is most often diagnosed in younger people. Chemotherapy is the main treatment. Some people need to have a stem cell transplant.

Anaemia, raised WBC count, low platelet (platelet may be variable) are known features of CML, splenomegaly (particularly if massive) is very suggestive of CML and Philadelphia chromosome is characteristic of CML.

The age supports the diagnosis of ALL along with the given clinical picture. A similar picture can be seen in aplastic anemia but meningitis supports more towards ALL (leukemic meningitis).

Hemophilia.

In Von Willebrands disease usually there is no hemarthrosis (except in type 3) and in hemophilia no nonblanching rash (there may be bruising). Isolated rise in APTT is highly suggestive of hemophilia (given case).

This is an ill-defined question and the likely diagnosis is hemophilia.

Smoking causes raised carboxyhemoglobin level causing hypoxemia and raised erythropoietin which leads to raised hemoglobin level (secondary polycythemia).

Raised hemoglobin, raised cell counts, and normal erythropoietin along with symptoms of hyperviscosity like headache and associated hypertension is diagnostic of polycythemia rubra vera.

Isolated thrombocytopenia and H/O prior URTI with development of purpura on the dependent areas of the body favours the diagnosis of ITP. In ITP, BT is prolonged which is present here.

The direct Coombs test is used to determine the cause of hemolytic anemia, like is it due to antibodies attached to RBCs which are seen in autoimmune -related hemolytic anemia.

Gastrectomy –> deficiency of intrinsic factor –> Vitamin B12 deficiency leading to macrocytic anemia and resulting subacute combined degeneration of cord causing loss of proprioception and loss of vibration sense.

Prolonged APTT and decreased factor VIII points towards the diagnosis of hemophilia A.

In hemophilia B there is factor IX deficiency. Haemophilia A is a genetic deficiency in clotting factor VIII, which causes increased bleeding and usually affects males. In the majority of cases it is inherited as an X-linked recessive trait.

A young boy with epistaxis and prolonged APTT is a probable case of hemophilia. Factor VIII and IX should be offerred to confirm the diagnosis.

Anemia of chronic disease is mostly normocytic and methotrexate causes folate deficiency which may lead to macrocytosis. So for this microcytic anemia NSAIDs induced GI hemorrhage is the most likely cause.

Disseminated intravascular coagulation (DIC) is characterized by systemic activation of blood coagulation, which results in generation and deposition of fibrin, leading to microvascular thrombi in various organs and contributing to multiple organ dysfunction syndrome (MODS). Consumption of clotting factors and platelets in DIC can result in life-threatening hemorrhage.

Usual lab reports are :

i) Platelets: Typically, moderate-to-severe thrombocytopenia is present in DIC.

ii) Bleeding time prolonged

iii) Global clotting times: (ie, activated partial thromboplastin time [aPTT] and prothrombin time [PT]) are typically prolonged.

iv) Assay for D-dimer : elevated.

Only anemia with macrocytosis is with normal examination findings make Megaloblastic aneamia to be the most likely cause where PBF shows hypersegmented neutrophils.

The picture fits two D/D.

1. Plummer Vinson syndrome

2. Oesophageal carcinoma.

Lower oesophageal stricture is more common in Ca. So presenting case is likely a case of Plummer-Vinson syndrome. It can be differentiated by the type of anemia. If it is IDA diagnosis is Plummer-Vinson syndrome.

Macrocytes are two types, round and oval. Oval macrocytes are seen in megaloblastic anemia which occurs due to Vit B12 and/or folic acid deficiency.

Glossitis (painful tongue), angular stomatitis, and smooth tongue are the characteristic feature of iron deficiency but are also known features of megaloblastic anemia. The absence of koilonychea also favours megaloblastic anemia.

G6PD (glucose-6-phosphate dehydrogenase) deficiency exacerbated by administration of oxidant drugs (e.g., primaquine, dapsone, quinidine). In active G6PD deficiency, Heinz bodies can be seen in red blood cells on a blood film.

IDA is one of the causes of generalized pruritus. Heavy periods, pallor and tiredness further supports the diagnosis.

Polycythemia.

Itching after hot shower; dizziness and angina due to hyperviscosity and splenomegaly are well-known features of polycythemia.

Fever and altered sensorium suggest the diagnosis of TTP. Also in TTP, there is fragmented RBC which is present here.

Thrombotic thrombocytopenic purpura leads to increased amounts of large von Willebrand factor which then attach to activated platelets and mediate further platelet aggregation.

Platelets end up being removed and the resulting fibrin 200 strand formation remains.

These fibrin strands along with the stress from the blood flow cause fragmentation of the red blood cells, leading to schistocyte formation.

There are low platelet counts.

Low MCV (range for MCV is 80-96 fL), angular stomatitis, red tongue, and koilonychia are characteristic of iron deficiency anemia.

Feeling tired all the time and prolonged periods suggest anemia. So serum Hb should be done initially.

The age of the patient and pancytopenic picture give us a clinical diagnosis of Aplastic anemia. Normal WBC morphology rules out ALL, AML, and pernicious anaemia while the age rules out CML as a diagnosis.

Folate deficiency.

Zieve's syndrome is an acute metabolic condition that can occur during withdrawal from prolonged alcohol abuse. It is defined by hemolytic anemia, hyperlipoproteinemia, jaundice, and abdominal pain. The underlying cause is liver delipidization.

Iron deficiency Anemia (IDA).

S/S pallor, koilonychia, angular stomatitis, atrophic glossitis, marked Anemia ( Cardiac enlargement, Flow Murmurs, ankle oedema and heart failure)

Investigation :

Microcytic hypochromic anemia

Serum ferrtitin level reduced

Anisocytosis, and poikilocytosis

Total iron binding capacity is increased.

Treatment: Iron supplementation with B12 and folic acid.

Haemoglobin of the donor meets the minimum requirement for donation.

If syncope then we can continue donating giving simultaneous normal saline to the donor.

Haemoglobin of the donor meets the minimum requirement for donation as it is routinely done in every donor prior to donation and therefore this has no impact on syncope.

ALL is more common in childhood while AML is in adults.

Features are very similar so to differentiate clinically is very difficult.

Diagnosis can be confirmed by bone marrow biopsy.

Failure of beta chain production

Haemarthrosis causing disability makes the likely diagnosis of hemophilia.

2-3

Features are suggestive of multiple myeloma. Bone marrow aspirate will show plasma cell infiltrate (60% or more plasma cells in bone marrow).

Removal of hormonally active tumor

Small cells with round nucleus and scant indistinct cytoplasm (Lobular carcinoma)

Ovarian ca is the likely diagnosis for which tumour marker is CA 125.

Low serum Na, low serum osmolarity, and high urine osmolarity.

The diagnosis is lower respiratory tract infection in association with neutropenia resulting from chemotherapy. Treated with broad-spectrum antibiotics. For chemotherapy-induced neutropenia GCSF (granulocyte colony stimulating factor) is given subcutaneously.

Diagnostic cell in Hodgkin's disease is Reed-Sternberg cells.

The diagnosis is multiple myeloma.

i) age 60 yrs

ii) pathological rib fracture (from metastases)

iii) recurrent infection (due to B cell dysfunction (manifested as hypogammaglobulinemia), numerical and functional abnormalities of T cells, and dysfunction of natural killer cells)

iv) raised calcium levels.

There are abundant plasma cells in the bone marrow.

IV antibiotics.

Pneumonia should be treated first.

Oesophageal carcinoma.

There is dilatation in the oesophagus which is seen both in achalasia and carcinoma. Dysphagia to solid initially is very much suggestive of carcinoma and also Barrett’s change is a clue to carcinoma.

Asbestos exposure is a risk factor for lung cancer and also has a synergistic effect with cigarette smoke. Horseness can be from the involvement of recurrent laryngeal nerve.

Increased thirst, confusion, and drowsiness are features of hypercalcemia. Any solid organ tumour can produce hypercalcemia. Here treated Ca breast is the probable cause of hypercalcemia.

Tamoxifen can promote the development of endometrial carcinoma. So vaginal bleeding will be of concern for us.

The mentioned lump in the left supraclavicular region is Virchow’s gland, and has long been regarded as strongly indicative of the presence of cancer in the abdomen, specifically gastric cancer.

Gastric carcinoma.

[i) blood group A is associated with gastric cancer

ii) vomiting, tiredness, and weight loss are general features of gastric cancer

iii) palpitation from anemia of cancer

iv) hepatomegaly (metastasis) and ascites are late features of gastric cancer.

v) palpable left supraclavicular mass- is Virchow’s gland, has long been regarded as strongly indicative of gastric cancer.

Paraneoplastic syndrome.

Features given are well-known features of autonomic neuropathy which can be a result of paraneoplastic syndrome.

Diencephalon is made up of four distinct components:

i) the thalamus

ii) the subthalamus

iii) the hypothalamus and

iv) the epithalamus.

Among these the hypothalamus has a crucial role in causing urinary frequency.

High fiber diet.

Except high fiber diet all others are risk factors for developing rectal carcinoma.

Here only two points are mentioned- cervical lymphadenopathy and splenomegaly!

This combination makes NHL the most likely cause though splenomegaly is a relatively uncommon feature of it. This combination does not fit in other options.

Here patient's WBC is <2800, i.e. patient has leucopenia (probable neutropenia).

Piperacillin/Tazobactam may be used in the management of neutropenic patients with fever suspected to be due to a bacterial infection as in patients with post chemotherapy neutropenia. Even febrile neutropenia can be seen in patients with cancer per-se!

Squamous cell laryngeal cancer.

Chronic hoarseness is the most common early symptom.

Other symptoms of laryngeal cancer include pain, dysphagia, a lump in the neck, sore throat, earache, or a persistent cough. Patients may also describe breathlessness, aspiration, haemoptysis, fatigue, and weakness, or weight loss. 

There is weight loss and there is an opacity in the right upper mediastinum. This may indicate an enlarged lymph node or lymphoma causing pressure on the right recurrent laryngeal nerve resulting in hoarseness. As CT didn't reveal any bronchial lesion and no breathing difficulty it is unlikely to be a bronchial pathology. So CT-guided lymph node biopsy can reveal the diagnosis.

In males osteoporotic fracture is less common. As the patient had prostatic malignancy pathological fracture from secondary metastasis to bone (here vertebra leading to paraplegia) is more common.

The patient is immunocompromised with a high fever (40C) suggestive of infection. Broad-spectrum IV antibiotics should be started empirically while waiting for blood reports.

Patients on steroids develop suppression of hypothalamic pituitary adrenal axis and frequently may lead to adrenal insufficiency (here vomiting, abdominal pain, and sudden falls in the morning secondary to postural hypotension on getting up from bed points towards the diagnosis of adrenal insufficiency).

Pain ear and discomfort during swallowing, ulceration at the back of the tongue, and palpable non-tender cervical lymph node are suggestive of oropharyngeal malignancy. Acute mastoiditis and tonsillitis will not cause tongue ulcers. Similarly, dental abscesses will not cause tongue ulcers. In herpes zoster pain and vesicle will be in the affected nerve distribution.

Age, altered bowel habits, bleeding per rectum, and isolated ulcer on sigmoidoscopy suggest colorectal cancer.

Hypercalcemia is common in squamous cell carcinoma.

CA 125 = ovarian cancer; CA 153 = cancer breast; CA 19-9 = pancreatic cancer; CEA = colorectal carcinoma; AFP = hepatocellular carcinoma.

CA 125 is tumour marker for ovarian tumour.

In cancer patient obstruction does not respond to medical treatment and hence diagnostic and therapeutic laparotomy is the option of choice.

Pancoast tumour.

Hoarseness of voice is due to compression of the recurrent laryngeal nerve, ptosis due to compression of the sympathetic ganglion, palpable mass in the right supraclavicular fossa due to involvement of the supraclavicular lymph node. History of smoking and given picture indicates the diagnosis of Pancoast tumour.

For cancer or chemotherapy-induced vomiting ondensatron is the drug of choice. As here vomiting is intractable IM ondensatron should be given not oral.

Stenting

The likely cause is malignant stricture for which endoscopic biopsy is the definitive investigation.

Neuropathy is a common side effect of chemotherapy.

Chemotherapy can damage nerves that affect feeling and movement in the hands and feet. Doctors call this condition chemotherapy-induced peripheral neuropathy (CIPN). Symptoms can be severe and may affect a person's quality of life.

Sinus squamous cells ca

Nasal obstruction, and epistaxis are features of nasopharyngeal carcinoma; with cranial nerve palsy, diplopia due to 6th nerve, (also 5th and 12th cranial nerves are frequently affected) otalgia and conductive deafness from local extension, as mentioned, can occur.

Younger age of onset and relieved with aspirin favours the diagnosis of osteoid osteoma.

Smoking history, chest signs, and Horner’s syndrome points towards lung cancer (probable pancoast tumour).

Mass in ascending colon and anaemia make cecal carcinoma the likely diagnosis from the given options.

The likely diagnosis is lung cancer, so the best investigation for this is LN biopsy.

Large cell carcinoma is, by definition, a poorly differentiated malignant epithelial tumor. It consists of sheets or nests of large polygonal or giant multinuclear cells.

FNAC

Likely diagnosis is small cell lung cancer causing SIADH and resulting in hyponatremia.