HEMOSTATIC DISORDERS;

QUANTITATIVE AND QUALITATIVE

DISORDERS
ANTOLIN, Reina Alexa/Chan, Arizalyn/Pajo,Darwin/Ricardos, Denee Anne/Zapatero,Ericka
 DISORDERS OF PRIMARY HEMOSTASIS
BASIC TERMINOLOGY FOR CLINICAL FINDINGS IN BLEEDING DISORDER
• Petechiae- purplish red, pinpoint hemorrhage spots in the skin
caused by loss of ability to withstand normal blood pressure and
trauma
• Purpura- hemorrhage of blood into small areas of skin, mucous
membranes, and other tissues
• Ecchymosis- form of purpura in which blood escapes into large
areas of skin or mucous membranes, but not into deep tissues
• Epistaxis- nosebleed
• Hemarthrosis- leakage of blood into a joint cavity
• Hematoma- a swelling of tumor in the tissues or a body cavity that
contains clotted blood
• Hematuria- intact red cells in the urine
• Hemoglobinuria- refers to hemoglobin(no intact red cells) in urine
• Hemoptysis- expectoration of blood secondary to hemorrhage in the
larynx, trachea, bronchi, or lungs
• Melena- stool containing dark red or black blood
• Menorrhagia- excessive menstrual bleeding
DISORDERS OF HEMOSTASIS
A. VASCULAR CONNECTIVE TISSUE DEFECTS
1. HEREDITARY CONNECTIVE TISSUE DEFECTS
a. Ehlers-Danlos Syndrome
- Autosomal dominant pattern of inheritance
 Clinical Findings:
 Hyperextensible joints and hyperplastic skin
 Connective tissue of skin, vasculature, and bones is adversely affected
leading to lack of structural support and great tissue fragility
 (+) large skin ecchymosis and hematomas, gum bleeding, excessive
postpartum bleeding, and GI bleeding; (+)easy bruisability
 Laboratory Findings:
 Coagulation test- Normal
 Platelet Function Test- Normal
b. Pseudoxanthoma elasticum
-Rare; autosomal recessive
-Connective tissue elastic fibers in small arteries are
calcified andstructurally abnormal
Clinical Findings:
 Hemorrhagic episodes
Subarachnoid and GI bleeding- Most common cause of death
c. Marfan Syndrome
-Autosomal dominant
-Decreased vascular elasticity
-Characterized by long extremities, dislocated lenses and aortic
root dilation
-Arachnodactyl (Spider fingers)
2. ACQUIRED CONNECTIVE TISSUE DEFECTS
a. Vitamin c Deficiency (Scurvy)
-Vitamin C is important for the formation of the intact structure of the
vascular basement membrane
Clinical Findings
Gum Bleeding and subcutaneous tissue and muscle hemorrhage;
(+) petechiae particularly around the hair follicles. Large
hemorrhagic areas may develop below the eyes particularly in
infants.
Clinical Findings
Anemia
Low ascorbic acid level
(+) Tourniquet test
b. Senille Purpura
-Acquired and chronic disorder of the elderly due to aging process
that leads to the degeneration of collagen, elastin, and
subcutaneous fat.
 Clinical Findings
(+) red to purple ecchymosis on the forearm, back of the hand
and neck secondary to loss of skin and vascular elasticity
Brownish discoloration are probably Hb is not properly removed by
the macrophage system
3. HEREDITARY ALTERATIONS OF VESSEL WALL STRUCTURE
a. Hereditary Hemorrhagic Telengiectasia
- Autosomal dominant
- Characterized by vascular malformations and surface skin
lesions called telangiectasia. Small blood vessel are focally
disorganized and dilated throughout the body with poor support;
the ability to contract is diminished
Clinical Findings:
Telengiectasia are thin dilated vessels and permanent
Lesions range from pinpoint to 3mmand are red to violet.
Has possibility to bleed spontaneously or from minor trauma
Usually appears on the face, lips, tounge, mucous membranes of
the mouth and nose, ears, conjunctivae, and the palms and soles.
Frequent epistaxis and anemia
 Laboratory Findings:
Anemia- usually IDA due to bleeding
Bleeding time- Normal
Platelet function test- Normal
Tourniquet test- Normal
Coagulation test- Normal

b. Congenital Hemangiomata (Kasabach-Merritt Syndrome)

4. ACQUIRED ALTERATIONSOF VESSEL WALL STRUCTURE

a. Diabetes Mellitus
b. Amyloidosis
5. ENDOTHELIAL DAMAGE
A. Autoimmune vascular purpura
- Drug induced purpura
- Allergic purpura
 Autoimmune
 Purpuric eruptions that begins as a small round, raise, pink areas on
the skin surface accompanied by swelling and some cases of ulcers.
Lesions turn dark red and begin to fuse within hours.
- Henoch-Schonlein purpura
 Allergic purpura with abdominal pain and joint (knees, ankles, and
wrists).
b. Infectious purpura
- Purpura may be due to several causes:
 Inflammatory response to infection
 Autoimmune process
 Bacterial products or toxins
 Direct injury
 B. Platelet Disorders

Definition of terms:
• Thrombocytopenia- Decreased platelet count
• Thrombocytosis- Increased platelet count
• Thrombocythemia- Fixed increase in circulating platelets
associated with myeloproliferative disease. Markedly Increased
platelet count; abnormal function
• Thrombsathenia- Functionally abnormal platelets (no fibrinogen
receptor)
• Thrombocytopathia/Thrombocythopathy- Functionally
abnormal platelets due to defective platelet factor 3.

•
 1. Quantitative Disorders

a. THROMBOCYTOPENIA
1. Decreased platelet production
Megakaryocyte hypoproliferation
-Aplastic anemia
Ineffective thrombopoiesis
Marrow replacement
-Myeldysplastic syndrome
2. Decreased platelet survival time
 Increased platelet destruction
-Idiopathic thrombocytopenic purpura
-Thrombotic thrombocytopenic purpura
- Hemolytic uremic syndrome
- Disseminated intravascular coagulation- mass consumption of
platelets
- Mechanical destruction- artificial heart valves
3. Increase platelet sequestration
Splenomegaly
Myelofibrosis

4. Dilution of platelet count (Dilutional Thrombocytosis)

Extensive blood transfusion
The degree of thrombocytopenia is directly proportional to the
number of units transfused.
STORED BLOOD CONTAIN NONVIABLE PLATELETs
b. Thrombocytosis
1. Primary (automonous) thrombocytosis
Unregulated production of megakaryocytes in bone marrow
- Essential Thrombocythemia
-Chronic Myelogenous leukemia
- Polycythemia vera
- Other myeloproliferative disorders
Platelet count usually greater than 1000 x 109/ L (moderately increased)
2. QUALITATIVE DISORDER

a.Inherited
. 1. Platelet adhesion defects
 Bernard-Soulier Syndrome
- Deficiency of Ib/IX/V on platelet surface- prevents platelet
interactionwith vWF
Laboratory Findings
Giant platelets greater than 20um with dense granulation
Increased closure time
Platelet aggregation test- subnormal with ristocetin
 von Willebrand deficiency
-Deficiency with vWF
-Most common Inherited bleeding disorder
-Autosomal dominant
- Platelets cannot adhere to collagen to form platelet plug
 Clinical Findings
 Mucocutaneous bleeding ranging from mild to severe
 Laboratory Findings
 Platelet count- Normal
 Closure time: Normal or Increased
 Platelet aggregation: abnormal with ristocetin
 Prothrombin time: Normal
 aPTT: Normal or Increased
 Factor VIII: Normal or decreased
 vWF:Ag- Decreased
 Classification of von Willebrand disease
1. Type 1- Partial quantitative deficiency of vWF
2. Type 2
a. Qualitative deficiency of vWF
2a- Decreased platelet- dependent vWV function
2b- Increased affinity for platelet glycoprotein Ib
2M- decreased platlet-dependent vWF function
2N- Markedly decreased binding of VIII to vWF
3. Type 3- Complete deficiency of vWF
 Laboratory Findings
 Platelet aggregation test- Abnormal with ristocetin
2. Platelet Aggregation Defect
Glanzmann’s thrombasthenia
-Deficiency or abnormality of platelet membrane gb Iib/Iia
-Fibrinogen cannot attach to platelet surface and initiate platelet
aggregation
Laboratoory Findings
Platelet aggregation test: abnormal with ADP, collagen,
epinephrine
Increased closure time (PFA)
3. Platelet Granules Secretion Defect
 Gray platelet syndrome
-Deficiency of dense granules and lack ADP release
Laboratory Findings
Platelet aggregation test- Abnormal secondary aggregation w/ ADP
and epinephrine
 Hemansky-pudlack
Wiskott-Aldrich
Chediak-Higashi anomaly
b. Acquired
1. Uremia
2. Myeloprofilerative disorders
3. Praproteinemias
4. Cardiopulmonary bypass
5. Aspirin intake
-Inhibits cyclooxygenase
-Abnormal platelet aggregation with ADP, collagen and
epinephrine
 DISORDERS OF SECONDARY HEMOSTASIS
Most common inherited coagulation disorders
1. von Willebrand disease (categorized under primary hemostasis disorder)
2. Hemophilia A
- Factor VIII deficiency
- Second Most common Inherited bleeding disorder
- X-linked recessive
- Occurs primarily in males
- Mothers are carriers
Clinical Findings:
Platelet count- Normal
aPTT- Increased
Factor VIII- Decreased
3. Hemophilia B
- Factor IX deficiency
- X-linked recessive
Clinical Findings
same as hemophilia A
Laboratory Findings
Platelet count- normal
PT- Normal
aPTT- Increased
Factor IX- decreased
 Clinical Manifestation of Coagulation Factor
Deficiencies
Type of Bleeding Coagulation Factor Defciency
Easy Bruising II, VIII, IX
Hematomas II, VIII, IX
Mucosal Bleeding II, VIII, IX, XI
Hemarthrosis VIII, IX, X
Postsurgical bleeding Fibrinogen, II, V, VII, VIII, IX, X, XI, XIII
Intracranial bleeding VII, VIII, IX, XIII
Delayed wound healing Fibrinogen, XIII
Umbilical cord bleeding X, XIII
Miscarriage Fibrinogen, XIII
Thrombosis Abnormal fibrinogens
Asymptomatic XII, prekalikrein, HMWK
 Disorders Of Coagulation Causing Clotting Factor Deficiencies
Factor Inherited Coagulopathies Acquired Coagulopathy
Pattern of Inheritance Coagulopathy
I Autosomal recessive Afibrinogenemia Severe liver disease
Diffuse Intravascular
coagulation
Autosomal dominant Dysfribinogenemia Fibrinolysis
II Autosomal recessive Prothrombindeficiency Liver disease
Vitamin K Deficiency
Anticoagulant Therapy
V Autosomal recessive Factor V deficiency Severe liver disease
(OWREN’s disease, labile Diffuse Intravascular
factor deficiency) coagulation
Parahemophilia Fibrinolysis
VII Autosomal recessive Factor VII deficiency Liver disease
Vitamin K Deficiency
VIII X-linked Recessive Hemophilia A Diffuse Intravascular
coagulation
Fibrinolysis
Autosomal dominant vWF
IX X-linked Recessive Hemophilia B Liver disease
Vitamin K Deficiency
X Autosomal recessive Factor X Deficiency Liver disease
Vitamin K deficiendy
Anticoagulant therapy
XI Autosomal recessive Hemophilia C- Rosenthal
Syndrome
(common in Eastern
European Jewish
descent)
XII Autosomal recessive Factor XII deficiency

XIII Autosomal recessive Factor XIII deficiency Liver Disease

Diffuse Intravascular
coagulation
Fibrinolysis

Prekallikrein Autosomal recessive Fletcher Trait

HMWK Autosomal recessive Fitzgerald Trait