W04 - HAEM: Haemostasis; Thrombotic Disorders; Bleeding Disorders Flashcards
Discuss how to approach a bleeding disorder.
Hx:
?Bruising
Epistaxis
Post-surgical bleeding
Menorrhagia
Post-partum haemorrhage
Post-trauma
Outline the symptoms and treatment of haemophilia and Von Willebrand’s disease.
Haem. A (VIII) and B (IX)
X-linked
Identical phenotypes, B less severe
Severity of bleeding depends on the residual coagulation factor activity
*Haemarthrosis
*Muscle haematoma
*CNS bleeding
*Retroperitoneal bleeding
* Post surgical bleeding
VwB Disease
(vWF), helps to prolong the life of factor VIII in the clotting cascade, commonest inherited coagulopathy
* mucosal bleeding, spontaneous etc.
> factor infusions, fresh frozen plasma or cryoprecipitate.
> desmopressin in haemophil.
Discuss other congenital clotting factor and platelet abnormalities.
1) ITP
Immune thrombocytopenia (ITP) is a type of platelet disorder
may be triggered by infection with HIV , hepatitis or H. pylori
> Steroids, IV IgG, Thrombopoietin analogues
> Splenectomy (rare)
2) LIVER FAILURE
Factor I, II, V, VII, IX, X, XI
Prolonged PT, APTT Reduced Fibrinogen
Cholestasis - Vit K dept factor deficiency
Factor II, VII, IX, X
3) Haemorrhagic Disease of the Newborn
Immature Coagulation Systems
Vitamin K deficient diet (esp Breast)
Fatal and incapacitating haemorrhage
> Completely preventable by administration of vitamin K at birth (I.M vs P.O)
Discuss the symptoms, causes and management of thrombocytopenia.
Decreased production Marrow failure
Aplasia
Infiltration
Increased consumption Immune ITP
Non immune DIC
Hypersplenism
Presentations:
Petechia
Ecchymosis
Mucosal Bleeding
Rare CNS bleeding
> hydroxycarbamide and aspirin is given in high risk cases (elderly, platelets >1500×109/l or previous thromboembolic events)
Low-dose asprin alone in lower risk patients
interferon given in pregnancy
> tranexamic acid
steroids. (imm med.)
TPO agonist
BM Transplantation
Discuss acquired causes of haemostatic failure.
Thrombocytopenia
Liver failure
Renal failure
DIC
Drugs Warfarin, Heparin, Aspirin, Clopidogrel, Rivaroxaban, Apixaban, Dabigatran, Bivalirudin ……..
Acquired clotting factors deficiencies
Haemophilia A & B Dx & Mgmt
Clinical
Isolated prolonged APTT
Normal PT
Reduced FVIII or FIX
Genetic analysis
> Coagulation factor replacement FVIII/IX
DDAVP (Desmopressin)
Tranexamic Acid
Prophylaxis in severe
> Splints
Physiotherapy
Analgesia
Synovectomy
Joint replacement
VwB Disease Dx & Mgmt
Type 1 quantitative deficiency = [vwf]
Often autosomal dominant
Type 2 (A,B,M,N) normal [vwf] but qualitative deficiency determined by the site of mutation in relation to vWF function
Type 3 severe (complete) deficiency
- recessive
> vWF concentrate or DDAVP
Tranexamic Acid
OCP etc
Haemophilia A & B Complications
Synovitis
Chronic Haemophilic Arthropathy
Neurovascular compression (compartment syndromes)
Other sequelae of bleeding (Stroke)
Describe how blood clots.
Platelets => adhere, activate, aggregate
Adherence facilitated by:
GP1b binds vWF
GP1a
Activation facilitated by:
ADP => COX => aggregation
Aggregation facilitated by:
Thomboxane A2 (via arachadonic acid catalysed by COX)
- Primary Haemostatic Plug
- Definitive = fibrin formation
- prothrombin => thrombin (Xa)
- Fibrinogen => Fibrin (Thrombin)
Understand factor that influence whether blood is hyper- or hypo-coagulable.
a
Understand the main tests of coagulation, especially the PT and APTT.
1) PT = evaluates ability to clot (INR standardises across labs)
* Warfarin is monitored by using the prothrombin time (PT), which is expressed as the INR. The dose of warfarin is adjusted to give an INR of 2-4
= measure of extrinsic pathway
2) APTT = determines efficacy of therapy
* Heparin is measured using the aPPT. This is the activated partial thromboplastin time. This measures the intrinsic and common pathways.
Mediators of Fibrinolysis
activators of plasminogen = t-PA, u-PA
plasminogen => plasmin => fibrin degradation
Drugs targeting ADP pathway
Antithrombotics include
- Clopidogrel
- Prasugrel
- Ticagrelor
Drugs targeting GP 11b/IIIa pathway
Antithrombotics include
- Abciximab
- Tirogiban
- Eptifibatide
Drugs targeting COX pathway
Antithrombotics include
- Aspirin which prevents arachadonic acid => TxA2
