haematology

Question 1

Amyloidosis is a group of conditions caused by the deposition of extracellular insoluble fibrins in organs and blood vessels
Clinical features

Answer 1

Patients may present with features affecting multiple organs, such as:

The kidneys, with nephrotic syndrome/renal failure.
The gastrointestinal system, with macroglossia, malabsorption, or hepatosplenomegaly.
The neurological system, with neuropathies.
The vasculature, with periorbital purpura (racoon eyes).
Or the joints, with painful asymmetrical large joint inflammation.

Question 2

diagnosis - Amyloidosis

Answer 2

iagnosis

The diagnosis of amyloidosis requires tissue biopsy and apple-green birefringence when stained with Congo red and viewed under polarised light. Biopsy is often taken from the rectum (has sensitivity of 74–94%).

Question 3

Anaemia of chronic disease

Answer 3

Malignancy
Chronic infections such as TB
Connective tissues disease such as rheumatoid arthritis

Question 4

Aplastic anaemia

diagnosis

Answer 4

diagnosis is made by at least 2 of the following:

Anaemia: haemoglobin <10 g/dL
Thrombocytopenia: paltelets <50 x 10^9/L
Neutropenia: absolute neutrophil count <1.5 x 10^8/L

Question 5

Clinical features of Fanconi’s anaemia

Answer 5

in Fanconi’s anaemia: pigmentation abnormalities, hearing defects, renal abnormalities, genital abnormalities, solid tumours, and short stature.

Question 6

Basophilic stippling

Answer 6

It is seen in megaloblastic anaemia, thalassaemias (in particular alpha thalassaemia), sideroblastic anaemia and alcohol abuse. A rare cause is the inherited disorder pyrimidine 5’-nucleotidase deficiency.

Question 7

Howell Jolly Bodies

Answer 7

Howell Jolly Bodies are remnants of the red blood cell nucleus, typically removed by the spleen.

Their presence on a blood film suggests hyposplenism, which can be either functional (with the spleen in situ) or true (associated with splenectomy).

Question 8

Schistocytes definition and causes

Answer 8

Schistocytes are fragments of red blood cells seen in microangiopathic haemolytic anaemia (MAHA).

MAHA may be isolated, or associated with thrombotic microangiopathy syndromes (such as haemolytic uraemic syndrome and thrombotic thrombocytopenia purpura) or disseminated intravascular coagulation (DIC).

Question 9

Left shift definition and causes

Answer 9

Left shift is primarily seen in acute infection
Severe left shift (with the presence of myelocytes, promyelocytes and blasts) is more suggestive of myeloproliferative disorders such as chronic myeloid leukaemia, myelofibrosis or acute leukaemia.

Question 10

Anisocytosis

Answer 10

most common cause of anisocytosis with a low mean corpuscular volume is iron deficiency,

Question 11

Cabot rings d

Answer 11

red blood cell inclusions of unknown origin. They are slender loops seen in the cytoplasm of red cells in megaloblastic anaemia, severe anaemia of any cause, lead poisoning and leukaemia.

Question 12

Echinocytes or burr cells (

Answer 12

Causes include: liver disease, vitamin E deficiency, end-stage renal disease, and the haemolytic enzyme disorder pyruvate kinase deficiency.

Question 13

Complications of blood transfusions

Allergy

Answer 13

Allergy (features and management)
Presentation ranges from urticaria to angioedema and anaphylaxis. Management: stop the transfusion, give saline, Adrenaline (if anaphylactic), Chlorphenamine, and Hydrocortisone.

Question 14

Acute haemolytic transfusion reaction

Complications of blood transfusions

Answer 14

Caused by giving an incompatible blood bag to a patient. Early signs include fever, hypotension, and anxiety. Late complications include generalised bleeding secondary to disseminated intravascular coagulation (DIC).
Management: stop the transfusion, give saline, treat DIC.

Question 15

eFbrile non-haemolytic transfusion reaction

Complications of blood transfusions

Answer 15

Presents with fever, rigors/chills, but patients are otherwise well.
Management: slow the transfusion, give Paracetamol.

Question 16

Transfusion-related acute lung injury

Answer 16

Presents with pulmonary oedema and can cause acute respiratory distress syndrome (ARDS).
Management: stop transfusion, give saline, treat ARDS.

Question 17

Investigations DVT

Answer 17

D-dimer

Generally used in situations where there is a low probability of DVT.
Is highly sensitive but not specific which means that it can only reliably exclude VTE and does not confirm it.
Other common conditions which may raise the D-dimer include malignancy, infection, pregnancy, stroke, myocardial infarction and aortic dissection.
Doppler ultrasound

Typically considered the investigation of choice for diagnosis.
Patients with high probability of DVT will normally have a Doppler ultrasound without the need for a D-dimer first.
Although highly sensitive and specific it is not the gold-standard investigation because DVTs can be missed if image quality is suboptimal.
Digital subtraction or CT/MR venogram

All three can be used to evaluate the extent of a DVT and look for rare underlying causes such as May-Thurner syndrome.
Digital subtraction venography is technically the gold-standard investigation but is rarely used due to it’s highly invasive nature.

Question 18

Disseminated intravascular coagulation (DIC

Answer 18

Clinical features

Patients present with excess bleeding e.g. epistaxis, gingival bleeding, haematuria, bleeding from cannula sites. Patients may also present with fever, confusion, or coma.

This is often in the context of severe systemic disease

Physical signs include petechiae, brushing, confusion, and hypotension.

Question 19

Disseminated intravascular coagulation (DIC rf

Answer 19

Risk factors

Major trauma or burns
Multiple-organ failure
Severe sepsis or infection.
Severe obstetric complications
Solid tumours or haematological malignancies
Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia that is associated with DIC. This comes up frequently in written exams

Question 20

Essential thrombocytosi

Answer 20

myeloproliferative disorder caused by dysregulated megakaryocyte (platelet precursor) proliferation.

Clinical features

50% of patients are asymptomatic, and diagnosed after an incidental blood test. The hallmark is an increased platelet count (>450 x 10^9/L).

JAK2 V617F mutation is present in 50-60% of patients with essential thrombocytosis, and helps distinguish essential thrombocytosis from secondary (reactive) thrombocytosis.

Question 21

Pancytopenia definition

Answer 21

Pancytopenia is diagnosed by a full blood count showing the combination of: anaemia, thrombocytopenia, and leukopenia.

Question 22

Causes of pancytopaenia

Answer 22

Causes of decreased marrow haematopoetic function

Common causes include chemotherapy and radiotherapy (the pancytopenia may be transient).
Vitamin B12 and folate deficiency.
Marrow infiltration by haematological malignancies (leukaemias or lymphomas).
Myelofibrosis, in which there is progressive marrow fibrosis.
Multiple myeloma (a plasma cell dyscrasia).
Parvovirus infection in haemolytic disease (such as sickle cell anaemia).
Inherited causes of marrow failure

The most common causes include Fanconi’s anaemia (an autosomal recessive condition) and dyskeratosis congenita (an X-linked condition).
Increased destruction/sequestration of blood cells peripherally

This is seen in conditions affecting the liver (such as hepatitis B/C, autoimmune hepatitis, and cirrhosis).
Immune destruction of blood cells
This occurs in drug-induced pancytopenia (secondary to, for example, Sulphonamide or Rifampicin).

Question 23

Causes of agranulocytosis

Answer 23

ssociated with depleted levels of basophils and eosinophils.

Drug causes:

Carbamazepine
Carbimazole
Clozapine

Question 24

Causes of lymphocytosis

Answer 24

Acute viral infection (especially EBV and CMV)
Chronic atypical infection (tuberculosis, brucella, toxoplasmosis)
Lymphoproliferative disorders (chronic lymphocytic leukaemia and lymphoma).

Question 25

Hereditary spherocytosis

Answer 25

utosomal dominant condition, seen in northern European populations, caused by mutations in structural red cell membrane proteins. linical features of Hereditary spherocytosis It typically presents with neonatal or childhood onset jaundice/anaemia, and splenomegaly. Management of Hereditary spherocytosis If mild, patients may be managed conservatively with folic acid supplementation. If severe, splenectomy before the age of 5 years is essentially curative.

Question 26

Warm autoimmune haemolytic anaemia (AIHA) pathophysiology

Answer 26

Warm AIHA is an IgG mediated extravascular haemolytic disease in which the spleen tags cells for splenic phagocytosis Causes of warm AIHA Idiopathic Lymphoproliferative neoplasms (CLL and lymphoma) Drugs including methyldopa SLE

Question 27

Cold autoimmune haemolytic anaemia (AIHA) pathophysiology

Answer 27

Cold AIHA is an IgM-mediated haemolytic disease in which IgM fixes complement causing direct intravascular haemolysis (also known as cold agglutinins) Causes of the cold AIHA: Idiopathic Post-infectious haemolytic anaemias: occurring 2-3 weeks after infection (examples include EBV and mycoplasma)

Question 28

Clinical features of Haemophilia A

Answer 28

X-linked recessive inherited bleeding disorder caused by deficiency in clotting factor VIII It typically presents early in life with deep and severe bleeding into soft tissues, joints and muscles. Diagnosis of Haemophilia A Diagnosis is with a factor VIII assay, and severity depends on the factor VIII level (severe disease occurs if factor VIII is <1% of normal). Management of Haemophilia A Minor bleeds can be managed with Desmopressin and major bleeds with recombinant factor VIII.

Question 29

Haemophilia B inheritance and pathyophysiology

Answer 29

Hemophilia B is an x-linked recessive inherited bleeding disorder caused by deficiency in clotting factor IX – an integral part of the intrinsic component of the coagulation cascade (measured using the APTT). Clinical features of Haemophilia B It typically presents early in life with deep and severe bleeding into soft tissues, joints and muscles. Diagnosis of Haemophilia B Diagnosis is with a factor IX assay.

Question 30

Management of high INR | Major bleeding

Answer 30

``` Major bleeding Stop anticoagulants Administer IV vitamin K Administer fresh frozen plasma or prothrombin complex Minor bleeding ```

Question 31

Management of high INR | Minor bleeding

Answer 31

Stop anticoagulants Administer IV vitamin K Repeat INR after 24 hours, may need further vitamin K

Question 32

Management of high INR | No bleeding with INR > 8

Answer 32

Stop anticoagulants Administer IV or oral vitamin K Repeat INR after 24 hours

Question 33

Management of high INR | No bleeding with INR > 5

Answer 33

Withhold 1-2 doses of anticoagulant | Review maintenance dose of anticoagulant

Question 34

Hodgkin's lymphoma | Risk factors

Answer 34

Risk Factors Epstein Barr Virus HIV Immunosuppression Cigarette smoking

Question 35

Clinical features | Hodgkin's lymphoma

Answer 35

supraclavicular non-tender lymphadenopathy, Alcohol-induced pain is a suggestive symptom. ymptoms caused by compression of surrounding structures e.g. shortness of breath or abdominal pain. B symptoms (fever, night sweats, and weight loss

Question 36

Hodgkin's lymphoma diagnosis

Answer 36

Diagnosis Lymph node biopsy with evidence of Reed Sternberg cells is diagnostic. Blood results can predict a poor prognosis via low haemoglobin and raised LDH, as they indicate high red cell turnover. Staging scans are required to elucidate the extent of disease. Management Treatment is usually with chemoradiotherapy.

Question 37

Investigations | myeloma

Answer 37

Work-up investigations Basic bloods: FBC may show anaemia, U&E may show renal impairment (particularly raised serum creatnine), hypercalcaemia is a common feature. Skeletal survey: this is typically done with X-ray but CT/MRI is more sensitive. Findings include osteolytic bone lesions and pathological fractures. Diagnostic investigations Serum and/or urine electrophoresis: this will show a paraprotein spike (typically IgG). Serum free light chain essay (Bence Jones protein): in myeloma serum free light chain levels are high. This can be used in the 1-2% of patients with non-secretory multiple myeloma (i.e. those that are negative for serum/urine monoclonal protein on electrophoresis). Tissue diagnosis typically by bone marrow aspirate and biopsy: myeloma is confirmed if there are >10% of plasma cells in the bone marrow. Investigations to inform prognosis CRP (the higher the level, the worse the prognosis) LDH (the higher the level, the worse the prognosis) Beta-2 microglobulin (a very high over very low level confers poor prognosis) FISH and cytogenetic analysis (this may also inform the type of treatment used)

Question 38

arget INR for different diseases

Answer 38

Important target INRs to remember include: For patients with atrial fibrillation: 2-3 For patients with metallic valve replacements: 2-3 (aortic valve) 2.5-3.5 (mitral valve) Following venous thromboembolism (VTE): 2-3

Question 39

Factor V Leiden features

Answer 39

inherited thrombophilia is factor V Leiden. This is caused by a mutation in clotting factor V, which becomes resistant to inactivation by protein C. Homozygosity increases the risk of VTE 50-fold and heterozygosity increases the risk 5-fold.

Question 40

Protein C deficiency features

Answer 40

Protein C (and its co-factor, protein S) inactivates clotting factors V and VIII. Inactivating mutations in protein C or S increase the risk of thrombosis. The prevalence is higher in Southeast Asian patients.

Question 41

Tumour lysis syndrome

Answer 41

Clinical features A common presentation would be e.g. 2 days after receiving high dose chemotherapy for acute leukaemia or lymphoma. Patients may present with dysuria/oliguria, abdominal pain, or weakness. Investigations Important investigations include: U&E (potassium and phosphate are typically raised), calcium (low), uric acid (raised), and ECG (metabolic abnormalities e.g. hyperkalaemia may precipitate life-threatening arrhythmias).

Question 42

Von Willebrand disease (VWD) is the most common inherited bleeding disorder.

Answer 42

Clinical features Excess or prolonged bleeding from minor wounds Excess or prolonged bleeding post-operatively Easy bruising Menorrhagia Epistaxis GI bleeding

Question 43

VWD) in investigations

Answer 43

Investigation results In VWD there is decreased factor VIII activity, so the PT time is normal but APTT is prolonged (if factor VII activity is <35% of normal). Bleeding time is prolonged. Subtypes of VWD Note that severity of symptoms depends on the type of VWD. Type 1 VWD is caused by a partial quantitative deficiency in VWF. Type 2 VWD is caused by qualitative defects in VWF (e.g. decreased adhesion to platelets or factor VIII). Type 3 VWD is caused by almost complete deficiency of VWF.