Clotting disorders

Key points

Clotting cascade summary

Extrinsic pathway (quick):

Endothelial damage - Tissue factor (3) + Factor 7 - Factor 10

Prothrombin Time: Measure of extrinsic and common pathway - tested with thromboplastin

Prolonged in Factor 7 and vitamin K deficiency, liver disorders

Intrinsic pathway (slow):

Endothelial collagen - Factor 12 - Factor 11 - Factor 9 - Factor 10

9+8+5 = prothrombinase

aPPT (Thromboplastin = Tissue factor and phospholipids): Measure of intrinsic and common pathway - tested with Ca, phospholipid, intrinsic pathway activator

Prolonged in vW disease, heparin use, intrinsic + common pathway factors

Factor 8 deficiency results in increased aPPT, not PT

Both PT + aPPT normal in factor 13 and a2 Antiplasmin deficiency, can be normal in vW disease

If both aPPT + PT long, do thrombin time:

Thrombin time test: Add thrombin to blood sample and check fibrin clot time

If normal = deficiency of thrombin e.g., Liver disease or warfarin

If long = deficiency of fibrinogen e.g., DIC, heparin, afibrinogenaemia

Fibrin + Factor 13 + Von Willebrand Factor (vWF) + factor 8 = platelet aggregation

Vitamin K dependent factors:

2, 7, 9, 10, protein C & S

Bleeding disorders

Haemophilia A: Factor 8 (80%, classic Haemophilia)

Haemophilia B: Factor 9 (20%, Christmas disease)

Mild (>5% deficiency) - Major trauma and surgical/dental procedures

Moderate (1-5% deficiency) - minor trauma

Severe (<1% deficiency) - Daily risk - needs factors prophylaxis

X linked recessive, but 1/3 are de novo mutations

Haemarthrosis, soft tissue haematomas

Joint deformities if untreated

May require portacath for regular factor infusions

Management if undergoing procedure

Haemophilia team liaison

Clotting factors on induction + factor assay

May stay in overnight for factor assays in am

Factor 8: half-life 8-12h

Factor 9: half-life 24h - need large doses

Aim to dose to 50% level

Recombinant activated factor 7 can be used for Haemophilia A and B patients that have inhibitors

May need fasciotomy for compartment syndrome caused by bleed

vW disease - bleeding mucosa + epistaxis. Autosomal dominant

Desmopressin causes release of vWF + VIII - therefore can be used to treat vWD and mild Haemophilia A

Factor 5 Leiden - Protein C cannot inactivate Factor 5 - causes thrombophilia

Platelet disorder - Petechia and purpura

Platelets needs glycoprotein Ib to bind vWF, IIb + IIIa to bind fibrin

Glycoprotein Ib is missing in Bernard Soulier syndrome

Glycoprotein IIb + IIIa is missing in Glanzmann thrombasthenia - serious, lifelong coagulopathy

Factor 13 deficiency - Bleeding from cord or unexplained intraventricular haemorrhage

Disseminated intravascular coagulation

Excessive thrombin generation - fibrinogen consumption - fibrin deposition in vessels - consumption of clotting and anticlotting factors + platelets

Test D-dimer: breakdown product of fibrin

Give fresh frozen plasma + platelets. Heparin and Anti-thrombin 3 not helpful

Recombinant factor 7a is now used in emergencies, refractory haemophilia

Immune thrombocytopaenia

Typically resolves in 3 months in 80%

Chronic after 12 months

IVIg + anti-D therapy

Splenectomy for bleeding complications or failed medical management

80% response rate

Anticoagulants

Heparin activates antithrombin III, reversed with protamine - monitor with Factor Xa levels

Warfarin inhibits production of Vitamin K dependent factors - reverse with Vitamin K or recombinant factors in emergency

Direct oral anticoagulants (Apixaban, rivaroxaban) inhibit factor Xa

Page edited by Mrs Charnjit Seehra BSc November 2024

References

Holcomb and Ashcraft’s Pediatric Surgery, 7th edition, 2020, Chapter 5

Julia S, James U. Direct Oral Anticoagulants: A Quick Guide. Eur Cardiol. 2017;12(1):40-45. doi:10.15420/ecr.2017:11:2