Haematology: Pathology - Bleeding disorders Flashcards
What does PT measure?
Prothrombin time assesses the extrinsic and common coagulation pathways
Prolonged PT is caused by deficiency/dysfunction of which coagulation factors?
Factor V
Factor VII
Factor X
Prothrombin (factor II)
Fibrinogen
What does PTT measure?
Partial thromboplastin time assesses the intrinsic and common coagulation pathways
Prolonged PTT is caused by deficiency/dysfunction of which coagulation factors?
Factor V
Factor VIII
Factor IX
Factor X
Factor XI
Factor XII
Prothrombin (factor II)
Fibrinogen
Interfering Ab to phospholipid
What is bleeding time?
An older test of platelet function which measures the time taken for a standardised skin puncture to stop bleeding
What effect will nonthrombocytopaenic purpuras have on platelet count, bleeding time, and tests of coagulation (PT, PTT)?
All will be normal
List eight types/causes of nonthrombocytopaenic purpuras
- Infection (e.g. meningococcaemia)
- Drug reactions
- Scurvy
- Ehlers-Danlos syndrome
- Cushing syndrome
- Henoch-Schonlein purpura
- Hereditary haemorrhagic telangiectasia
- Perivascular amyloidosis
At what platelet level does spontaneous bleeding occur?
<20,000 platelets/uL
At what platelet level does aggravation of post-traumatic bleeding occur?
20,000-50,000 platelets/uL
What effect will thrombocytopaenia have on platelet count, bleeding time, and tests of coagulation (PT, PTT)?
Reduced platelet count
Increased bleeding time
Normal PT and PTT
What is the main clinical concern with severe thrombocytopaenia?
Spontaneous intracranial haemorrhage
Four broad causes of thrombocytopaenia
- Decreased platelet production
- Decreased platelet survival
- Increased platelet sequestration
- Platelet dilution
Give five causes of decreased platelet production with an example of each
- Selective impairment: e.g. drug- or infection-induced (alcohol, measles)
- Nutritional deficiencies: e.g. B12/folate
- Bone marrow failure: e.g. aplastic anaemia
- Bone marrow replacement: e.g. leukaemia, disseminated cancer
- Ineffective haematopoiesis: e.g. myelodysplastic syndromes
What causes ITP?
Ab to platelets (may recognise self Ag, autoantibodies, or non-self Ag, alloantibodies)
Give three examples of secondary causes of chronic ITP
HIV
SLE
B-cell neoplasms (e.g. CLL)
What are autoantibodies in chronic ITP most commonly directed towards?
Glycoprotein IIb-IIIa or Ib-IX
Usually IgG
What are the common treatments for chronic ITP?
Glucocorticoids (relapse common)
Splenectomy
IVIg
Rituximab (anti-CD2O Ab)
What is the difference in terms of clinical presentation and course in acute vs chronic ITP?
Acute: usually children, symptoms appear abruptly and typically following viral illness, self-resolve within 6 months
Chronic: usually adult women <40yo, insidious onset, does not resolve without treatment
Are splenomegaly and lymphadenopathy typical features of chronic ITP?
No: should prompt consideration of other diagnoses (e.g. B-cell neoplasm)
Name four common drug causes of drug-induced thrombocytopaenia
Vancomycin
Quinine
Quinidine
Heparin
Type I vs type II HIT
Type I: occurs rapidly after onset of therapy, little clinical significance, sometimes resolves despite continuation of therapy, most likely due to direct platelet-aggregating effect of heparin
Type II: 5-14 days after onset of therapy, leads to life-threatening venous and arterial thrombosis, caused by Ab that recognise complexes of heparin and platelet factor 4 (Ab binds and causes platelet activation), risk reduced with use of LMWH
Pentad of TTP (thrombotic thrombocytopaenic purpura). How does this differ from HUS?
- Fever
- Thrombocytopaenia
- Microangiopathic haemolytic anaemia
- Transient neurologic deficits
- Renal failure
HUS does not present with neurologic symptoms, has more prominent renal failure, and presents mostly in children
What are the two thrombotic microangiopathies?
- TTP (thrombotic thrombocytopaenic purpura)
- HUS (haemolytic-uraemic syndrome)
Deficiency of what enzymes causes TTP?
ADAMTS13 (may be inherited or acquired via autoantibodies)
What causes typical HUS? What is the pathogenesis?
Shiga-like toxin from E. coli O157:H7 causes endothelial damage leading to platelet activation and aggregation
What are the three causes of atypical HUS?
Defects in:
1. Complement factor H
2. Membrane cofactor protein (CD46)
3. Factor I
What effect do thrombotic microangiopathies have on platelet count, bleeding time, and tests of coagulation (PT, PTT)?
Platelet count reduced
Increased bleeding time
Normal PT and PTT
List two clinically significant acquired defects of platelet function
- NSAIDs: decreased platelet aggregation through COX inhibition
- Uraemia: defective platelet adhesion, granule secretion, and aggregation
What clotting factor is deficient in haemophilia A?
Factor VIII
What clotting factor is deficient in haemophilia B?
Factor IX
What is the most common inherited bleeding disorder in humans?
Von Willebrand disease
What is the usual inheritance pattern of vWD?
AD
What effect does von Willebrand disease have on platelet count, bleeding time, and tests of coagulation (PT, PTT)?
Normal platelet count
Increased bleeding time
Normal PT
Normal or increased PTT
What is the relationship between vWF and factor XIII?
vWF binds and stabilises factor VIII
What is the most common hereditary disease associated with life-threatening bleeding?
Haemophilia A
How is haemophilia A inherited?
X-linked recessive (males at increased risk)
How is von Willebrand disease treated?
Desmopressin (which stimulates vWF release) or plasma can be give pre-procedure
How is haemophilia A treated?
Recombinant factor VIII
What is Christmas disease?
Haemophilia B
What is the effect of haemophilia on PT and PTT?
Normal PT
Increased PTT
How is haemophilia B inherited?
X-linked recessive (males at increased risk)
How is haemophilia B treated?
Recombinant factor IX
What is the most common site of thrombi in DIC?
Brain
What is the difference in clinical presentation between acute and chronic DIC?
Acute: bleeding diathesis
Chronic: thrombotic complications
