Clotting/Coagulation disorders:

Question 1

Hemophilia - Factor VIII deficiency:

Answer 1

• Classic hemophilia (hemophilia A)
• X-  linked disorder (affects males)
• Most common - severe bleeding
•Spontaneous hematomas <  1, 5, 75%
• Diagnosis 
- factor VIII assay
• Treatment 
- factor VIII concentrate
• Large number of hemophiliacs contracted AIDS from 
poor screening

Question 2

Hemophilia - Factor IX Deficiency:

Answer 2

• Factor IX is Christmas factor
• Christmas 
disease (Hemophilia B)
• X-  linked recessive disorder 
• Indistinguishable from classic hemophilia 
• Requires evaluation of factor VIII and IX activity 
levels to diagnose
• Treatment 
- factor IX concentrate

Question 3

Von-Willebrand Disease

Answer 3

• Coagulation + Platelet disorder
• Congenital
• Deficiency of vWF molecule 
• Part of Factor VIII, 
• Mediates platelet 
adhesion
• Prolonged Bleeding time
• Low Factor VIII 
• Mucocutaneous bleedin

Question 4

Alterations of Platelets and Coagulation:

Answer 4

Hemostasis is dependent on adequate numbers of platelets and levels
of coagulation factors.
• Diminished hemostasis results in either internal or external
hemorrhage.
• Diffuse hemorrhage into skin tissues that is visible through the skin
causes a red-
purple discoloration identified as a
purpura
• Thromboembolic disease
• Clotting disorders

Question 5

Disorders of Platelets

- Thrombocytopenia

Answer 5

•Thrombocytopenia
Platelet count <100,000/mm
3
• <50,000/mm3: hemorrhage 
from minor trauma
• <15,000/mm3:  spontaneous bleeding
•<10,000/mm3:  severe 
bleeding that can be fatal
•Example - Heparin-induced: immune-mediated
, adverse drug reaction caused by IgG antibodies 
against the heparin
-platelet factor 4; can lead to thrombosis; must stop heparin

Question 6

Disorders of Platelets

(Cont.)- Thrombocythemia:

Answer 6

• Thrombocythemia
• Also called thrombocytosis
• Platelet counts: >450,000/mm3
• Cause: accelerated 
platelet production in the bone marrow
•Types: 
primary 
or secondary (reactive) 
• Causes intravascular clot formation (thrombosis), hemorrhage, or other 
abnormalities

Question 7

Alterations of Platelet Function:

Answer 7

• Qualitative alterations
• Increased bleeding time in the presence of a normal platelet count
• Clinical manifestations
• Petechiae; purpura; pulmonary mucosa, gingival, GU, GI, and gum bleeding
• Disorders can be congenital or acquired.
• Causes of acquired
• Drug effects
• Systemic inflammatory conditions
• Hematologic conditions

Question 8

Alterations of Platelet Function (Cont.)

Answer 8

• Prolonged bleeding can result from alterations in platelet function.
• Adhesion between platelets and the vessel wall
• Platelet
-platelet adhesion
• Platelet granule secretion
• Arachidonic acid pathway activity
• Membrane phospholipid regulation

Question 9

Disorders of Coagulation

Answer 9

• Causes: defects or deficiencies of clotting factors
• Vitamin K deficiency
• Liver disease
• Cardiovascular abnormalities
• Vasculitis
• Impaired hemostasis

Question 10

Disseminated Intravascular Coagulation:

Answer 10

• Complex, acquired disorder: clotting
and hemorrhage simultaneously
occur
•Sepsis, cancer or acute leukemia, trauma, blood transfusion
•Cause: variety
of clinical conditions that release tissue factor
• Causes an increase in fibrin and thrombin activity in the
blood
• Produces augmented clot formation and accelerated
fibrinolysis

Question 11

Disseminated Intravascular Coagulation

Cont.

Answer 11

• Characterized by a cycle of intravascular clotting, followed by active
bleeding
• Is caused by the initial consumption of coagulation factors and
platelets
• Results from abnormally widespread and ongoing activation of
clotting
• Hemorrhage:
is secondary to the abnormally high consumption of clotting
factors and
platelets
• Deposition of fibrin clots in the circulation interferes with blood flow, causing
widespread organ hypoperfusion

Question 12

Disseminated Intravascular Coagulation

Cont.

Answer 12

• Clinical manifestations demonstrate wide variability.
• Bleeding from venipuncture sites
• Bleeding from arterial lines
• Bleeding from surgical wounds
• Purpura, petechiae, and hematomas
• Symmetric cyanosis of the fingers and toe

Question 13

Disseminated Intravascular Coagulation

(Cont.):

Answer 13

Treatment
• Eliminate underlying pathology 
• Control thrombosis
• Maintain organ function
• Administer replacement therapy
• Replace anticoagulants

Question 14

Thromboembolic Disease:

Answer 14

• Results from a fixed (thrombus) or moving (embolus) clot that blocks
flow within a vessel
• Denies nutrients to tissues distal to the
occlusion
• Death can result when clots obstruct blood flow to the heart, brain, or lungs.
• Arterial thrombi:
defects
in proteins involved in hemostasis
• Venous thrombi: variety
of clinical disorders or conditions

Question 15

Thromboembolic Disease

Cont.

Answer 15

Treatment
• Anticoagulants (heparin, coumadin)
• Thrombolytic (streptokinase, urokinase)
• Virchow triad
• Injury to the blood vessel endothelium: 
atherosclerosis, many others
• Abnormalities of blood flow
• Hypercoagulability of the blood

Question 16

Thromboembolic Disease

Cont.

Answer 16

• Hypercoagulability (thrombophilia)
• Individual is at risk for thrombosis.
• Primary (hereditary) vs.
secondary (acquired)
• Primary:
defects in proteins that are involved in hemostasis.
• Secondary:
condition or disease that promote venous stasis.
• Results from a deficiency of anticoagulation protein

Question 17

Hereditary Thrombophilias

Answer 17

• Inherited conditions increase risk for thrombosis.

* Most are autosomal dominant