HEMOSTATIC DISORDER

I. CONGENITAL HEMORRHAGIC DISORDER

A. Hemophilia A (factor VIII deficiency) and
Hemophilia B (factor IX deficiency)
1. Pathophysiology :
X chromosome, gene defect.
2. Clinical features :
mild, moderate and severe disease
3. Diagnosis :
a. screening tests
b. specific factor assay

4. Therapy : to raise the deficient factor

a. Pharmacologic therapy :

1. Hemophilia A : Desmopressin (dDAVP)

2. Hemophilia B : no effective drugs
b. Replacement therapy :
1. Beware of adverse effects
2. The choice of blood product is critical

c. Treatment options :
1. Fresh frozen plasma (FFP)
2. Cryoprecipitate
3. Factor concentrates
5. Complication : Arthropathy, Inhibitors,
Liver disease, HIV infection.
6. Interdisciplinary care hemophilia center
medical care, psychosocial care and
genetic counseling

B. von Willebrands disease

1. Physiology of vWF :
- HMW glycoprotein, 250 kD
- In plasma and in platelets
- as a carrier protein for coag. F VIII
- important for primary hemostasis
- mediates adhesion of platelets to the s.endot
- vWF F VIII complex : F VIII : C, F VIII : Ag,
F VIII : Cag, F VIII : RCof.

2. Clinical features : >> mucous membrane

bleeding, epistaxis, menorrhagia
3. Diagnosis :
- Combination of prolonged BT and a
decreased F VIII : C level classically
- Combination of abnormalities of the functional
measures of the vWF F VIII complex

variants of vWF (see table 2)

- Ristocetin aggregation
- Diff. of type F VIII multimer analysis :
type I, IIA, IIB, IIC, III.

Table 2. Laboratory Findings in Hemophilia A

and Severe vWF Disease
Labotatory test
Bleeding time
VIII : C
VIII : Ag
VIII : RCof

Finding
Hemophilia A
vWF disease
Normal
Prolonged
Decreased
Decreased
Normal
Decreased
Normal
Decreased

4. Therapy
a. dDVAP
b. Cryoprecipitate
c. F VIII concentrates

C. Other inherited factor deficiencies

1. F XII, prekallikrein and HMWK
2. F I, II, V, VII, X, XI and XIII

II. ACQUIRED HEMORRHAGIC DISORDER

A. Vitamin K deficiency
1. Etiology
a. dietary deficiency
b. malabsorption
c. antibiotic therapy
d. hemorrhagic disease of the new born
2. Clinical features : severe bruising or
excessive bleeding or asymptomatic

3. Diagnosis
- severe : prolonged PT and PTT
- early or milder def. : prolonged PT
4. Therapy
- Parenteral vit. K
- FFP
B. Liver disease
1. Etiology
a. decreased synthesis of coag. factors
b. Vit. K def

c. Functionally abnormal fibrinogens

d. Disseminated Intravasc. Coagulation
(DIC) and consumption of coag. factors
2. Clinical features
- vary with the course of the patients liver
disease
- >> GIT bleeding
3. Diagnosis
- Lab. findings varies widely

4. Therapy
- trial of parenteral vit K therapy
- Replacement therapy FFP
C. Clotting factor inhibitors autoantibodies
1. Inhibitors in hemophilia
2. Inhibitors in patients without preexisting
bleeding disorders
a. Etiology : drugs, autoimmune or
lymphoproliferative disorders,
spontaneous a.coagulants

b. Diagnosis : mixing study, factor assays

c. Therapy : supportive
3. Lupus anticoagulant cardiolipin
a. Prolonged PTT, false + serologic test
b. associated with recurrent spont.abortions.

COAGULATION REGULATION
AND
HYPERCOAGULABLE STATES

I. CONTROL MECHANISMS IN COAGULATION

A. Naturally occuring a.coagulants
1. Antithrombin III (AT III) acts as a serine
protease inhibitor
2. Protein C, Protein S Vit K dependent
3. Other plasma protease inhibitor : heparin
cofactor II, 2- macroglobulin.

B. Fibrinolitic system
1. Activation :
a. Intrinsic activation : a poorly understood
mechanism of activation
b. Extrinsic Activation : Tissue plasminogen
activator (t-PA), urokinase
c. Exogeneous (therapeutic) activation :
streptokinase, urokinase and t-PA

2. Sites of action
a. Fibrinogen
b. Fibrin
II. THROMBOTIC DISORDER
A. Congenital thrombotic disorder
1. AT III deficiency
2. Protein C deficiency
3. Protein S deficiency

B. AQUIRED THROMBOTIC DISORDER

THROMBOEMBOLIC DISEASE
1. Risk factors :
a. abnormalities of blood flow
b. abnormalities of the vasculature
c. abnormalities of the coagulation system
2. Clinical manifestations :
a. Venous thrombosis
- superficial thrombosis
- deep vein thrombosis

b. Pulmonary embolism
c. Arterial thrombosis
d. Other
4. Therapy
a. Agents treatment and prevention
1. Anticoagulants :
- Heparin
- Warfarin
2. Thrombolytic agents :
- Streptokinase
- Urokinase
- t-PA

b. Treatment approaches
1. Deep vein thrombosis : >> heparin,
thrombolytic agent
2. Pulmonary embolus : heparin, thrombolytic
agent
3. Myocardial infarction : thrombolytic agent
4. Peripheral artery and catheter thrombosis :
thrombolytic agent.

III. THROMBOHEMORRHAGIC DISORDER

A. Disseminated intravascular coagulation(DIC)
1. Pathophysiology (see table 3)
a. Initiation : pathologic activation of
the coag. cascade
b. Thrombosis
c. Consumption
d. Fibrinolysis
e. Hemolysis

Table 3. Conditions that commonly precipitate DIC

Infectious condition
Gram negative septicemia
Other endotoxin-related condition
Obstetric conditions
Abruptio placentae
Amniotic fluid embolism
Retained dead fetus
Vascular conditions
Aneurysm
Giant cavernous hemangioma
Hematologic conditions
Massive hemolysis
Promyelocytic leukemia
Snake venom
Trauma

2. Clinical features varies widely

a. diffuse bleeding from multiple sites
b. thrombotic lessions
3. Diagnosis lab. findings vary with time &
circumstances
Severe DIC :
a. Thrombocytopenia
b. Prolonged PT, PTT, TT
c. Decreased fibrinogen
d. FSPs
e. Microangiopathic hemolytic anemia

4. Therapy :
a. Low grade DIC treatment may not
be necessary
b. Clinically significant bleeding
replacement of depleted coagulation
factors and cells
c. Thrombosis : heparin

B. Thrombotic thrombocytopenic purpura

(TTP) and hemolytic-uremic syndrome
(HUS)
C. Heparin thrombocytopenia

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