HAEM - bleeding disorders Flashcards
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)
Clinical Px of haemophilia A
–Hemarthrosis
–Subcutaneous and intramuscular haematomas
–Psoas and retroperitoneal haematomas
–Traumatic bleeding:
•Bleeding from razor nicks is uncommon
•Delayed bleeding is common especially in tooth extractions, tonsillectomy
•Wound healing is slow in haemophiliacs
Which clotting profile would be abnormal in haeomphilia A?
APTT (factor 8 deficient)
INR is normal
Rx of haemophilia A
–Purified or Recombinant F VIII therapy
–Tranexamic acid
–Topical thrombin
–Role of FFP
Describe haemophilia B
- factor involved
- prevalance compared to haem A
- genetic
- Factor IX deficiency
- 4-8 times less common than Haemophilia A
- X-linked recessive
- Unlike Haemophilia A, spontaneous mutation rate is low, most patients have family history
- Severe disease manifests identical to Haemophilia A
Which factor is deficient in haemophilia A?
Factor 8
Which factor is deficient in haemophilia B?
Factor 9
Ix of haemophilia B
–Prolonged APTT (factor 9 deficiency), Normal INR
–APTT not sensitive to mild deficiency (F IX 20-30%)
Rx of haemophilia B
–Prothrombin complex
–Purified or Recombinant F IX
What is thrombocytopaenia?
deficiency of platelets in the blood.
This causes bleeding into the tissues, bruising, and slow blood clotting after injury
What are the causes of thrombocytopaenia?
- increased destruction
- decreased production
Increased destruction
- Auto-Immune:
- ITP
- SLE etc
- Drugs - Allo-immune:
- Post Transfusion Purpura
- Neonatal Allo-Immune Thrombocytopenia - Non-immune:
- Hypersplenism
- DIC / TTP / HUS
Decreased production
- Aplastic Anaemia
- Myelodysplasia
- Leukaemic infiltration
- Lymphoma infiltration
- Fibrosis
Where do you typically bleed in thrombocytopaenia?
•Skin and mucous membranes –Petechiae –Ecchymosis –Hemorrhagic vesicles –Gingival bleeding and epistaxis
- Menorrhagia
- Gastrointestinal bleeding
- Intracranial bleeding
(4) How do you assess the function of platelets?
- Thromboelastography (TEG)
- PLATELET AGGREGATION STUDIES
- ADP
- COLLAGEN
- ADRENALINE
- RISTOCETIN - Plt Function Analysis (PFA)
- Skin Bleeding Time: No longer preferred as technical issues of standardization and expertise
