1.Bleeding Disorders By Dr. Sabir M. Ameen

2. History

1. Site of bleeding:

* Muscle & joint bleeds indicate a coagulation defect

* purpura, prolonged bleeding from superficial cuts, epistaxis, GI bleeding, menorrhagia, indicate PLT disorder, thrombocytopenia or vW disease

3. History

2. Duration: congenital or acquired

3. Precipitating cause: if spontaneous indicate severe defect

4. surgery: dental extraction, tonsillectomy, circumcision. Bleeding immediately after surgery indicate defective PLT plug formation. Bleeding after some hours indicate failure of PLT plug stabilisation by fibrin due to coagulation defect.

4. History

5. Family history:

* Hereditary or acquired

* Negative history does not exclude a hereditary cause, as e.g: about 1/3 of cases of hemophilia have negative family history (mutations).

6. Systemic disease:

Hepatic or renal failure

CT disease

5. history

7. Drugs: almost any drug can potentially produce bleeding( cytotoxics. NSAIDsetc)

6. Examination

Look for: 1. anemia: BM failure, leukemia

2. purpura, bruises, bleeding in mouth

3. Telangiectasia of lips (HHT)

4. LN enlargement: leukemia, viral ( ITP)

5. Stigmata of chronic liver disease: spider nevi, clubbing, palmar erythemaetc

6. Fundal examination

7. Clinical Features of Bleeding Disorders Platelet Coagulationdisorders fac disorders Site of bleeding Skin Deep in soft tis. Mucous membranes (joints, musc) Petechiae Yes No Ecchymoses (bruises) Small, superficial Large, deep Hemarthrosis / muscle bleeding Extremely rare Common Bleeding after cuts & scratches Yes No Bleeding after surgery or trauma Immediate, Delayed1-2 d usually mild often severe 8. PlateletCoagulation Petechiae, Purpura Hematoma, Joint bl. 9. Petechiae Do not blanch with pressure (cf. angiomas) Not palpable (cf. vasculitis) (typical of platelet disorders) 10. Hemarthrosis 11. Hematoma 12. Petechiae 13. Purpura 14. Ecchymosis 15. Screening tests for bleeding disorders

TestAbnormality detected

Blood count andAnaemia, leukaemia, DIC

film

Platelet countThrombocytopenia

aPTTDef. of all coagulation factors except

VII, esp. follows VIII and IX; heparin

PTDef. of F I, II, V, VII, and X; warfarin

Thrombin time orHypo-, dysfibrinogenaemia; heparin

fibrinogenFDPs

Bleeding timeTest of platelet-vessel wall interaction

16. Causes of bleeding

1. Thrombocytopenia:

a- viral infections

b- drug-induced

c- B12 or folate deficiency

d- ITP, DIC, TTP/HUS ( consumption)

e- BM infiltration: leukemia, MM, Ca, myelofibrosis

17. Causes..cont.

2. Clotting factor deficiency:

a- liver disease

b- drugs: warfarin, heparin

c- consumption: DIC

d- dilution: massive blood transfusion

e- congenital: hemophilia..etc

f- vit K deficiency: e.g, malabsorption

18. Causescont.

3. CT atrophy:

a- old age

b- steroid therapy

c- wasting

4. Vessel wall disorders:

A- aspirin

B- Osler-Weber Rendu disease

C- angiodysplasia

19. Thrombocytopenia

The lifespan of a platelet is 7-10 days and the normal count for all ages is 150000-450000

Once released from the BM young platelets are trapped in the spleen for up to 36 hours before entering the circulation, where they have a primary haemostatic role.

Congenital abnormalities of platelets can be divided into disorders of platelet production and those of platelet function. All are very rare. In general they cause moderate to severe bleeding problems. 20. Acquired thrombocytopenia

Decreased productionof platelets due to suppression or failure of the BM is the commonest cause of thrombocytopenia. In aplastic anaemia, leukaemia and marrow infiltration, and after chemotherapy,thrombocytopenia is usually associated with a failure of red and white cell production but may be an isolated finding secondary to drug toxicity (penicillamine, cotrimoxazole), alcohol, or viral

infection (HIV, infectious mononucleosis). Viral infection is the most common cause of mild transient thrombocytopenia

21. Acquiredcont

Increased platelet consumptionmay be due to immune or non-immune mechanisms.

22.

Post-transfusion purpura (PTP)is a rare complication of blood transfusion. It presents with severe thrombocytopenia 7-10 days after the transfusion and usually occurs in multiparous women who are negative for the human platelet antigen 1a (HPA1a).

Antibodies to HPA1a develop, and in some way this alloantibody is responsible for the immune destruction of autologous platelets.

23.

Neonatal alloimmune thrombocytopenia (NAITP)is similar to haemolytic disease of the newborn except that the antigenic stimulus comes from platelet specific antigens rather than red

cell antigens. In 80% of cases the antigen is human platelet antigen 1a, and mothers negative (about 5% of the population) for this antigen form antibodies when sensitised by a fetus positive for the antigen. Fetal platelet destruction results from transplacental passage of these antibodies and severe bleeding, including intracranial haemorrhage, can occur in utero.

24.

Heparin-induced thrombocytopenia (HIT)occurs during unfractionated heparin therapy in up to 5% of patients, but is less frequently associated with low molecular weight heparins. It may become manifest when arterial or venous thrombosis occurs during a fall in the platelet count and is thought to be due to the formation of antibodies to heparin that are bound to platelet factor 4. The immune complexes activate platelets and endothelial cells, resulting in thrombocytopenia and thrombosis coexisting. Heparin-induced thrombocytopenia carries an appreciable mortality risk if the diagnosis is delayed.

25.

In thrombotic thrombocytopenic purpura (TTP)the presenting features can be fever, fluctuating neurological signs, renal impairment, and intravascular haemolysis, resulting in thrombocytopenia.

The condition is suspected clinically by thrombocytopenia, red cell fragmentation on the blood film, and a reticulocytosis.

26. Causes of acquired platelet dysfunction

Aspirin and NSAIDs

Penicillins and cephalosporins

Uraemia

Alcohol

Liver disease

Myeloproliferative disorders

Myeloma

Cardiopulmonary bypass

Fish oils

27. Increased consumption of platelets

Disorders with immune mechanism:

Autoimmune : ITP

Alloimmune : post-transfusion purpura, neonatal

alloimmune thrombocytopenia

Infection associated : infectious mononucleosis, HIV,

malaria

Drug induced : heparin, penicillin, quinine, rifampicin,

sulphonamides

TTP/HUS

Hypersplenism and splenomegaly

DIC

Massive transfusion

28. Treatment of platelet disorders

Congenital disorders:

Platelet transfusions (leucodepleted, HLA compatible and irradiated)

DDAVP

Tranexamic acid

Recombinant factor VIIa

Bone marrow transplantation

29. Treatmentcont

Acquired disorders

Bone marrow failure

Platelet transfusions if platelet count 10000

ITP (adults)

Prednisolone

Intravenous immunoglobulin

Splenectomy

Post-transfusion purpura

Intravenous immunoglobulin

Plasma exchange

Heparin-induced thrombocytopenia

Anticoagulation but without heparin

Thrombotic thrombocytopenic purpura

Large volume plasma exchange

Aspirin when platelets 50000

30. Treatmentcont

DIC:

Treat underlying cause

Fresh frozen plasma

Platelet transfusion

Hypersplenism

Splenectomy if severe

Platelet function disorders

Platelet transfusion

DDAVP

31. Idiopathic thrombocytopenic purpura(ITP)

It is due to auto- antibodies directed against PLT membrane glycoprotein IIb-IIIa which causes premature removal of PLTs by the monocyte-macrophage system

32. ITP

C/F: 1. in children: sudden onset of purpura, oral or nasal bleeding, usually 2-3 wk after a viral illness

2. In adults: affects females more, with insidious onset, usually not associated with viral infection, but may be associated with CT disease.

It is characterised by remission and relapse.

33. ITP

LAB.

1. CBC: reduced PLT count

2. BM: increased megakaryocytes

34. management

1. In children: usually it is self-limiting, if severe purpura or epistaxis, or PLT