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31

QUESTION 74
A 67-year-old diabetic man with atrial fibrillation is taking warfarin for primary prophylaxis and is
scheduled for inguinal hernia repair. His echocardiogram shows no structural abnormality. His
international normalised ratio (INR) is 2.9. Which of the following preoperative anticoagulant
management strategies is most appropriate?

A. Withhold warfarin therapy for four days before surgery and administer low-molecular-weight
heparin (LMWH) for these four days, ceasing 24 hours prior to surgery.
B. Withhold warfarin therapy four days before surgery and administer vitamin K1 on the eveningprior to surgery if his INR> 1.5.
C. Withhold warfarin for two days prior to surgery.
D. Continue warfarin up until the time of surgery then administer prothrombin complex
concentrate on the day of surgery.
E. Withhold warfarin therapy for four days before surgery. Commence intravenous infusion of
unfractionated heparin two days prior to surgery, ceasing four hours prior to surgery.

B

32

QUESTION 40
Poisoning with which of the following causes a shift in the Hb-oxygen dissociation curve to the left?
A. Carbon monoxide.
B. Cyanide.
C. Gamma-hydroxy-butyrate (GHB).
D. Methanol.
E. Aspirin.

A

33

A 74-year-old ex-smoking male with a history of ischaemic heart disease presents with a hip fracture requiring surgical fixation within a few days.  He is plethoric and there are no specific respiratory or cardiac abnormalities on examination.  Chest X-ray is normal and ECG shows left bundle branch block. 
 
His full blood count shows:  

  

Which one of the following would be the most appropriate initial therapy? 
 
A. Venesection. 
 
B. Intravenous radioactive phosphorus. 
 
C. Hydroxyurea. 
 
D. Therapeutic anticoagulation. 
 
E. Interferon α. 

A.  It is critical that the thrombocytosis and increased RBC mass is controlled pre-op otherwise the risk of arterial thrombosis is unacceptably high.

34

A 48-year-old previously well man, currently smoking 10 to 20 cigarettes/day, presents with the progressive onset over several months of lethargy and headache.  He takes no medications. 
 
Examination reveals him to be plethoric and hypertensive with no other significant findings. 
 
Full blood examination shows: 

  

Which one of the following would most strongly support a diagnosis of polycythaemia vera? 
 
A. Raised serum vitamin B12 level. 
 
B. Elevated total red cell mass. 
 
C. Normal marrow karyotype. 
 
D. Elevated serum uric acid level. 
 
E. Lowered serum erythropoietin level. 

Answer:  E

35

A 72-year-old man with a history of chronic obstructive pulmonary disease (COPD) presents with an intercurrent lower respiratory tract infection. Apart from plethora and pulmonary signs associated with his respiratory disease, no other abnormalities are found. 

Full blood examination shows: 

 

The most likely cause of the elevated haematocrit is: 

A. dehydration. 

B. chronic hypoxaemia. 

C. polycythaemia vera. 

D. spurious polycythaemia. 

E. low affinity haemoglobin. 

B.  The EPO level is raised.

36

What are the main features of polycythaemia vera?

- JAK2 mutation
- increased RBC mass
- Splenomegaly
- Normal arterial O2
- elevated WBC and platelets

37

What is the mechanism in polycythaemia vera?

Mechanism
Acquired JAK2 exon mutation (95% of cases) —> proliferation of all three haematopoietic cells lines (megakaryocytes, RBCs, myeloid) —> prominent overproduction of RBCs and to a lesser extent, WBCs and platelets w/ low EPO level.

38

What are the clinical findings in polycythaemia vera?

Clinical findings
Expanded blood volume & viscosity —> headache, dizziness, blurred vision, fatigue
Histamine release from basophilia —> fatigue
Epistaxis and GI bleeds —> abnormal platelet function and mucosal blood vessel engorgements
Plethora, engorged retinal veins
Splenomegaly
Thrombosis is major cause of morbidity and death - due to viscosity and abnormal platelets.  MUST control disease before any surgery

39

Epidemiology of polycythaemia vera?

Epidemiology
Men in their 60s, v rare under 40

40

What are the lab findings in polycythaemia vera?

Elevated HCT - >54/51% M/F respectively
Elevated RBC mass
Elevated WBC and PLT counts
Normal morphology of all three lines
Basophilia and eosinophilia
Low EPO levels
JAK2 mutation positive
BMBx - hyper cellular, panhyperplasia w/ absent iron stores (transferred to circulating RBCs)
Very high B12 due to secretion of transcobalamin III from WBCs
Hyperuricaemia
Iron deficiency from bleeding & phlebotomy - microcytosis w/ normal HCT
Elliptocytosis from progressive hypersplenism

41

What is the diagnostic criteria for polycythaemia vera?

Major Criteria (2 Mj + 1Mn or 1st Mj + 2Mn)
Hb more than 185 in men, 165 g  in women, or elevated red cell mass greater than 25% 
Presence of JAK2 617V greater than F or other similar mutations

Minor Criteria
BMBx: hypercellularity w/ prominent erythroid, granulocytic, and megakaryocytic proliferation.
Serum erythropoietin level below normal range.
Endogenous erythroid colony formation in vitro.

42

What is the differential diagnosis of polycythaemia vera?

Spurious - elevated HCT due to volume contraction / diuretis
Secondary 
- Hypoxia and smoking - carboxyhaemoglobin levels may be elevated 
- renal lesions (tumor, EPO secreting tumor (rare))
- Abnormal Hb (rare)
- CML if very high WCC
- Myelofibrosis if abnormal RBC morphology and nucleated RBCs
- ET is ultra high PLT count

43

What is the treatment of polycythaemia vera?

Phlebotomy to maintain HCT <45%, need should gradually decrease as iron stores diminish, avoid supplementation.
Decreases thrombotic complications
Low iron diet increases intervals between phlebotomy
If unable (high req, thrombocytosis, intractable pruritus) —> hydroxurea 1st, anagrelide 2nd
Reduction of platelet count reduces complications
Avoid alkylating agents - increases risk of conversion to acute leukaemia
All patients should receive aspirin, reduces thrombosis w/o risk of excessive bleeding
Allopurinol for hyperuricaemia
Antihistamines for itch, SSRIs if intractable

44

What is the prognosis of polycythaemia vera?

Indolent, median survival 11-15 years
Arterial thrombosis major cause of morbidity and mortality
May convert to myelofibrosis or CML
5% to AML (rare)

45

What is pseudohyperkalemia?

Pseudohyperkalemia is a rise in the amount of potassium that occurs due to excessive leakage of potassium from cells, during or after blood is drawn. 

Usually a lab artefact due to haemolysis during venepecture (excessive vacuum, too fine gauge), excessive tourniquet time, fist clench, delay in processing or tube dropping.

Also can occur in thrombocytosis (>500), leukocytosis (>70), or erythrocytosis (HCT >55%)

46

What are the features of essential thrombocythaemia?

Features
- elevated platelet count
- normal RBC mass
- absence of BCR-ABL gene
- uncommon

47

What is the mechanism of essential thrombocythaemia?

Mechanism
Unknown cause (high freq of JAK2 mutation) —> Proliferation of megakaryocytes —> thrombocytosis —> venous thrombosis

48

What is the epidemiology of essential thrombocythaemia?

Epidemiology
50-60 year olds, slightly more in women, rare

49

What are the clinical findings in essential thrombocythaemia?

Clinical findings
Discovery of elevated platelet count
Venous thromboses at unusual sights (i.e mesenteric, hepatic or portal vein
Erythromelalgia (painful burning of the hands)
Mucosal bleeding due to faulty platelets
Splenomegaly in at least 25%

50

What are the lab findings in essential thrombocythaemia?

Elevated PLT over 1-2000
Mildly elevated WBC w/ immature myeloid forms
Normal haematocrit
Smear:  Large platelets, but not giant or degranulated.  Normal RBC morphology
BMBx:  Megakaryocytosis w/ no other morphologic abnormalities
Cytogenetics:  Absent BCR-ABL (need to do to rule out CML)
JAK2 mutation in 50% of cases

51

What is the differential diagnosis of essential thrombocythaemia?

Reactive thrombocytosis —> PLT count not as high (less than 1000)
Inflammatory disorders (RA, UC, chronic infection)
Iron deficiency —> but thrombocytosis only if significant anaemia
Splenectomy → temporary thrombocytosis
PCV - no erythryocytosis
Myelofibrosis - normal RBC morphology, no nucleated RBCS, no giant degranulated platelets
CML - BCR ABL negative.

52

What is the treatment of essential thrombocythaemia?

Control platelet count w/ oral hydroxyurea, prevents thrombotic events w/o toxicity
2nd line anagrelide (low dose) - high dose = headache peripheral oedema and CHF
Vasomotor sx (erythromelalgia and parasthesias) —> aspirin
Low dose aspirin may reduce risk of thrombotic complications
Severe bleeding —> plateletpheresis

53

What is the prognosis in essential thrombocythaemia?

Prognosis
Indolent, high long term survival with control of thrombosis
Late:  fibrotic BM, massive splenomegaly and infarction
10-15% risk of progression to myelofibrosis, 1-5% risk of transformation to acute leukaemia 

54

A 62-year-old man with a history of controlled hypertension presents with worsening lethargy over several months and more recently, weight loss, night sweats and easy bruising.  Examination reveals anaemia, bruising and firm splenomegaly 12 cm below the left costal margin; no lymphadenopathy is evident. 
 
Full blood examination reveals: 

  

The blood film shows:
 
- teardrop poikilocytosis
- large degranulated platelet
- thrombocytopaenia
- nucleated RBC


The most likely diagnosis is: 
 
A. metastatic carcinoma. 
 
B. megaloblastosis. 
 
C. primary myelofibrosis. 
 
D. systemic lupus erythematosus. 
 
E. chronic myeloid leukaemia. 

C

55

What are the main features of myelofibrosis?

Features
 - striking splenomegaly
 - teardrop poikilocytosis
 - leukoerythroblastic bloods w/ giant abnormal plt
 - Hypercellular BM w/ reitculin or collagen fibrosis

56

What is the mechanism of myelofibrosis?

Mechanism
Increased secretion of platelet-derived growth factor —> bone marrow fibrosis —> extramedullary haematopoiesis (liver, spleen, LNs), reactivation of feral mesenchymal stem cells —> splenomegaly, leukoerythroblastic blood film w/ teardrop poikilocytosis —> anaemia, splenomegaly, BM failure

57

What is the epidemiology of myelofibrosis?

Epidemiology
>50, insidious

58

What are the clinical findings in myelofibrosis?

Fatigue due to anaemia
Abdominal fullness and early satiety due to splenomegaly
Massive splenomegaly
Hepatomegaly in >50% of cases
Late: progressive thrombocytopaenia due to BM failure
Painful episodes of splenic infarction
Severe bone pain - esp upper legs
Cachexia
Portal HTN w/ ascites and varices due to hepatic haematopoeisis
Occasionally: transverse myelitis due to epidural myelopoeises

59

What are the lab results in myelofibrosis?

Labs
Anaemia
Variable WCC (low/N/high)
Smear:  Significant poikilocytosis and teardrop RBCs, nucleated RBCs, left shifted myeloid series.  Bizarre giant degranulated platelets
Triad:  teardrop poikilocytos, leukoerythroblastic blood, giant abnormal platelets
BMBx:  Dry tap usually but if early: hyper cellular with reticulin fibres on silver stain demonstrating fibrosis.  Later:  Collagen, no precursors
JAK2 mutation in 65% of cases, MPL in 40%

60

What is the classic finding on blood smear in myelofibrosis?

Triad:  teardrop poikilocytos, leukoerythroblastic blood, giant abnormal platelets