1. BLEEDING DISORDERS

2. HEMOSTASIS-1
In health hemostasis ensures that the blood remains fluid and contained in the vasc.system.
If a vessel wall is damaged,a number of mechanisms are activated promptly to limit bleeding,involving:
1-Endothelial cells.
2-Platelets.
3-Plasma coag.factors.
4-Fibrinolytic system.

3. HEMOSTASIS-2
These activities are finely balanced between keeping the blood fluid and preventing intravasc.thrombosis.
1-Pimary hemostasis: vasoconstriction and platelet adhesion and aggregation leading to the formation of the platelet plug.
2-Secondary hemostasis: involves activation of coagulation system leading to the generation of fibrin strands and reinforce the platelet plug.
3-Fibrinolysis: activation of fibrin-bound plasminogen resulting in clot lysis.

4. ROLE OF ENDOTHELIAL CELLS IN HEMOSTASIS
Blood vessels are lined with endothelial cells,which synthesize and secrete various agents,that regulate hemostasis.
1-Procoagulant(prothrombotic) agents:tissue factor,von Willebrand factor,F V ,F VIII.
2-Anticoagulant (antithrombotic) agents:
prostacyclin,nitric oxide,endothelin-1.

5. ROLE OF PLATELETS IN HEMOSTASIS
Each megacaryocyte produces platelets.
remain in the circulation for about 10 days.
Activated platelets release the contents of stored granules into the blood plasma. The granules include, serotonin, platelet-activating factor (PAF), vWF, platelet factor 4, and thromboxane A2 , which, in turn, activate additional platelets
Platelet adhesion.
Platelet aggregation.

6. COAGULATION SYSTEM
Coag.factors: are plasma proteins synthesized in the liver which when activated lead to the deposition of fibrin.
1-Initiation phase: leads to the formation of the complex TF-VIIa.
2-Amplification phase: leads to the formation of a small amount of thrombin from prothrombin.
3-Propagation phase:leads to the formation of much larger amounts of fibrin.

8. Coagulation cascade Intrinsic system (surface contact)
Extrinsic system (tissue damage)
XII
XIIa
Tissue factor XI
XIa IX
IXa
VIIa
VII
VIII
VIIIa
Vitamin K dependant factors X Xa V Va II
IIa
IIa
(Thrombin)
Fibrinogen
Fibrin

9. INHIBITORS OF COAGULATION
Are proteins that inhibit activated procaogulation enzymes and prevent excessive intravasccular coagulation
Raised levels are not associated with bleeding.
Reduced levels may predispose to thrombosis.
Antithrombin.
Protein C,Protein S.
Tissue Factor Pathway Inhibitor (TFPI).

10. FIBRINOLYSIS Plasminogen Plasmin Fibrin FDPs
Small amouns of fibrin are constantly deposited within the vascular system and are removed by the fibrinolytic system.
Fibrinolysis is the process wherein a fibrin clot, the product of coaglation, is broken down.
Plasminogen Plasmin
Fibrin FDPs

11. HISTORY 1-Site of bleeding. 2-Duration of bleeding.
3-Precipitating cause.
4-Surgery.
5-Family history.
6-Systemic illnesses.
7-Drugs.

12. Clinical Features of Bleeding Disorders
Platelet Coagulation disorders factor disorders
Site of bleeding Skin Deep in soft tissues
Mucous membranes (joints, muscles)
(epistaxis, gum,
vaginal, GI tract)
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, Delayed (1-2 days),
usually mild often severe

13. Coagulation factor disorders
Inherited bleeding disorders
Hemophilia A and B
vonWillebrand disease
Other factor deficiencies
Acquired bleeding disorders
Liver disease
Vitamin K deficiency/warfarin overdose
DIC

14. Hemophilia A and B Hemophilia A Hemophilia B
Coagulation factor deficiency Factor VIII Factor IX
Inheritance X-linked X-linked
recessive recessive
Incidence 1/10,000 males 1/50,000 males
Severity Related to factor level
<1% - Severe - spontaneous bleeding
1-5% - Moderate - bleeding with mild
injury
5-25% - Mild - bleeding with surgery or
trauma
Complications Soft tissue bleeding

15. Clinical manifestations
hemophilia A & B are indistinguishable clinically
Hemarthrosis (most common)
Fixed joints
Soft tissue hematomas (e.g., muscle)
Muscle atrophy
Shortened tendons
Other sites of bleeding
Urinary tract
CNS, neck (may be life-threatening)
Prolonged bleeding after surgery or dental extractions

17. Disseminated Intravascular Coagulation (DIC)
Is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood vessels throughout the body. As the small clots consume coagulation proteins and platelets, normal coagulation is disrupted and abnormal bleeding occurs.
The small clots also disrupt normal blood flow to body organs which may malfunction as a result .

18. Depletion of platelets and coagulation factors
Systemic activation
of coagulation
Depletion of platelets
and coagulation factors
Intravascular
deposition of fibrin
Thrombosis of small
and midsize vessels
with organ failure
Bleeding

19. Common Clinical conditions associated with DIC
Sepsis
Trauma
Head injury
Fat embolism
Malignancy
Obstetrical complications
Amniotic fluid embolism
Abruptio placentae
Reaction to toxin (e.g. snake venom, drugs)
Immunologic disorders
Severe allergic reaction
Transplant rejection

20. Classification of platelet disorders
Qualitative disorders
Inherited disorders (rare)
Acquired disorders
Medications
Chronic renal failure
Cardiopulmonary bypass
Quantitative disorders
Abnormal distribution
Dilution effect
Decreased production
Increased destruction