HAEM - bleeding disorders Flashcards
(36 cards)
What does Activated Partial thromboplastin time (APTT) measure?
Intrinsic pathway coagulation (factors 8, 9, 11, 12)
Surface activating agent (Ellagic acid, kaolin)
Phospholipid
Calcium
What does Prothrombin time (PT) measure?
Extrinsic pathway (factor 7)
(remember PT is used for INR and INR is related to vitamin K & warfarin. Vitamin K helps produce factors 2, 7, 9, 10, and factor 7 is uniquely in EXTRINSIC - hence it measures extrinsic pathway)
What does Thrombin time measure?
Common pathway
(4) features of screening tests for hemostatic defects
- Platelet Count (150 - 400)
- Activated Partial Thromboplastin Time (Aptt) (24-32 Seconds)
- Prothrombin Time(pt)(10 -12 Seconds)
- Thrombin Time
How can you differentiate factor deficiency from presence of ‘inhibitor’ in coagulation?
Perform Mixing study:
Mix 1/2Pt + 1/2 Control (CONTROL - POOLED PLASMA from normal individuals) and perform APTT or PT
- If factor deficiency = APTT / PT will normalize (the control pool will make up for the deficiency)
- If ‘inhibitor’present = persistent abnormality (inhibitor will affect the control pool also)
(3) Causes of corrected APTT after Mixing study in previously normal PT, prolonged APTT
- Factor deficiency (VIII, IX, XI, XII)
- Early DIC
- Heparin Rx (variable correction)
(2) Causes of persistent abnormality after Mixing study in previously normal PT, prolonged APTT
- Lupus anticoagulant (common)
- Inhibitors towards specific coagulant factors VIII, IX, XI
(3) Causes of corrected PT after Mixing study in previously prolonged PT, normal APTT
- Factor deficiency (VII)-rare
- Liver disease, Vit K defi
- Warfain (above are common)
(2) Causes of persistent abnormality after Mixing study in previously prolonged PT, normal APTT
- Antiphospholipid ab’s: uncommon
- Antibodies to VII: rare
(2) Causes of corrected PT/APTT after Mixing study in previously prolonged PT, prolonged APTT
- Isolated deficiency in common pathway: Factors V, X, II, and fibrinogen
- Multiple factor deficiencies (common): Liver disease, vitamin K deficiency, warfarin, DIC
(3) Causes of persistent abnormality after Mixing study in previously prolonged PT, prolonged APTT
- Inhibitors towards V, X, II
- fibrinogen (rare)
- anti-phospholipid ab’s
(5) causes of prolonged PT
- Warfarin (F II, VII, IX, X)
- Liver disease
- Vitamin K deficiency
- DIC
- Factor VII deficiency
(7) causes of prolonged APTT
- Heparin anticoagulation therapy
- Liver disease
- Lupus anticoagulant
- DIC
- von Willebrand’s disease
- Haemophilia: Factor VIII, Factor IX deficiency
- Factor XII, XI deficiency
(3) causes of prolonged thrombin time (TT)
- DIC (decreased fibringogen)
- Liver disease
- Heparin
Describe purpuric disorders
- petechiae
- superficial echymoses
- haematoma & haemarthrosis
- late bleed
- gender
- FMHx
Purpuric disorders have characteristic petechiae, small & multiple superficial echmoses
- rare haematoma, haemarthrosis
- rare late bleed
- females > males
- variable FMHx
Describe coagulation disorders
- petechiae
- superficial echymoses
- haematoma & haemarthrosis
- late bleed
- gender
- FMHx
Coagulation disorders have rare petechiae, large & solitary superficial echymoses
- characteristic haematoma & haemarthrosis
- common late bleed
- 80-90% males
- common FMHx
(4) Common hereditary bleeding disorders
- Hemophilia – A /B
- Von Willebrand disease
- Factor deficiency
- Platelet Disorders
(5) common acquired bleeding disorders
–Liver disease –Vit K deficiency –DIC –Excessive anticoagulation –ITP (idiopathic thrombocytopaenic purpura)
(2) functions of vWF
- vWF mediates platelet adhesion at site of injury
- Stabilizes FVIII in circulation
Remember: Wherever platelet aggregation is needed, coagulation is also necessary. vWF is like a ‘taxi’ that carries fVIII to the proximity of a developing clot
What modifies penetrance of type I von Willebrand disease?
ABO group
- ABO glycosylation of vWF influences clearance
- People with non-O blood group have higher levels compared with O-group
- Blood group AB people have highest level
Describe type 1, 2, 3 of von Willebrand’s disease
Type 1 -partial quantitative deficiency of VWF
–70-80% cases- Ad
–Mild presentation / blood group.
Type 2 -qualitative deficiency of VWF
- Subtypes : Differences in multimers
- Mild to moderate bleeding.
- Abnormal Multimers
Type 3- virtually complete deficiency of VWF
All have prolonged APTT
Specific Ix for vWD (von Willebrand’s disease)
- von Willebrand Factor Antigen (vWAg)
- Factor VIII clotting activity : VIII C
- Functional assays : Ristocetin Co-Factor activity/Collagen-binding assay
Rx for vWD
- Desmopressin (DDAVP): Releasing FVIII & vWFAg from storage sites. Effective in Type 1.
- Replacement Therapy
- Antifibrinolytics - Tranexamic acid
- Fibrin Glue / Fibrillar collagen preparation
Explain pathophysiology of haemophilia A
- factors involved
- genetics
–Factor VIII deficiency
–F VIII normally circulates bound to vWf, which protects F VIII from proteolysis
Genetics:
–X-linked recessive (gene on X chromosome)
–Males present with features of disease (males = XY)
