Sunteți pe pagina 1din 31

Hematopathology Third Lab

25th Feb, 2012 27th Feb, 2012

Bleeding disorders

A review of the preview lecture

Bone marrow

Blood

Anemias

vs.
Polycythemia

Homeostasis (Hemostasis)

Homeostasis (Hemostasis)
hemostasis )himostsis, hmstsis( The termination of bleeding by mechanical or chemical means or by the complex coagulation process of the body, which consists of: (a) Vasoconstriction (b) platelet aggregation (c) thrombin and (d) fibrin synthesis. It is the arrest of the escape of blood by either natural means (clot formation or vessel spasm) or artificial means (compression or ligation)

Blood within the circulation must remain fluid, but if a blood vessel is damaged, localized coagulation must take place to prevent loss of blood. When there is injury to a blood vessel, a series of events is initiated which results in controlled hemostasis. 1 Local vasoconstriction 2 Adhesion and aggregation of platelets 3 Activation of the clotting cascade to form a fibrin clot 4 Activation of coagulation inhibitors (coagulation restricted to the site of injury) 5 Late fibrinolysis to restore patency of the vessel These complex interacting systems can be disturbed by: inherited factors or acquired factors .Resulting in bleeding or thrombotic disorders

Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, 7th ed. 2003 by Saunders

Common acquired coagulopathies: Disseminated intravascular coagulation Liver disease Vitamin K deficiency

History in a suspected bleeding disorder: Type of bleeding: mucocutaneous, hemarthroses/muscle hematomas Severity of bleeding: blood transfusions, anemia Previous tests of the hemostatic system Operations Dental extractions Trauma Childbirth Age of onset Family history Other medical problems Drugs: aspirin, non-steroidal anti-inflammatory drugs (NSAID).

Some Practical Points


Is the bleeding mucocutaneous (often seen in platelet defects and vWD).
or into joints and muscles (often seen in coagulation factor deficiencies)? The age of onset and a family history are important to address the issue of whether the condition is likely to be inherited or acquired.

Menorrhagia (beginning from the menarche) is much more likely to be due to an inherited coagulation defect than is menorrhagia (starting later in life). there is a family history, the mode of inheritance is important, for If example, X-linked recessive inheritance suggests hemophilia A or B.
The severity must be assessed; did it result in anemia or a blood transfusion?

Conditions which may be mistaken for a coagulopathy !!! Henoch-Schonlein vasculitis Vitamin C deficiency Steroid purpura/Cushings disease Amyloid in the skin vessels Ehlers-Danlos/pseudoxanthoma elasticum Cryoglobulinemia

Investigations in suspected abnormal bleeding Screening tests: Full blood count Prothrombin time Activated partial thromboplastin time Thrombin time or fibrinogen PFA100 closure or bleeding time Other first line investigations: Factor VIII, von Willebrand factor )vWF( activity, vWF antigen Platelet aggregation Platelet nucleotides Second line investigations: Factor XIII 2-antiplasmin

What mean by: (a) (b) (c) (d) PT PTT TT BT

vWD (AD)
vWD is a common disorder caused by (reduction or structural abnormality) of vWF. vWF has the dual role of promoting platelet adhesion to exposed collagen and protecting factor VIII in the circulation. In vWD, the main defect is the resulting abnormal platelet function and is manifest by mucocutaneous bleeding. Menorrhagia is common in affected women. Most cases are mild, with significant bleeding only occurring after a haemostatic challenge.

Interpretation of coagulation screening tests

PT prolonged, APTT normal: Deficiency of factor VII (seen in early vitamin K deficiency/oral anticoagulation or liver disease) PT normal, APTT prolonged: Deficiency of factors VIII, IX, XI (or the contact factors), Lupus anticoagulant PT prolonged, APTT prolonged (TT normal): Deficiencies of factors (II, V, X), Vitamin K deficiency/oral anticoagulation, Liver disease PT prolonged, APTT prolonged (TT prolonged): Afibrinogenemia Heparin DIC

Megakaryocytes
In stressed thrombopoiesis: cytoplasm matures quicker than nucleus so that low ploidy MK start to produce platelets that are larger, denser and metabolically more active

Each MK Can Produce 3000 Platelets

Thrombocytopenia

Production Aplastic anemia Leukemias Chemotherapy

Survival ITP Evans syndrome SLE DIC TTP/HUS Sepsis

BM infiltration

Loss from circulation Splenomegaly MassiveTransfusion

ITP

ACUTE
Childhood

CHRONIC
Adult

Peak Age Years Sex M/F Onset


Preceding Infection

26 1:1 Acute Common


Often <20,000/uL

20 40 1:3 Chronic Unusual


Often >20,000/uL

Platelet Count
Spontaneous Remission

> 80% 2 4 weeks

< 20%
Months/ Years

Usual Duration