MLAB 1227- COAGULATION

KERI BROPHY-MARTINEZCoagulation Disorders: Primary Hemostasis

CLINICAL MANIFESTATIONS OF BLEEDING DISORDERS Type of bleeding indicates which component of the

hemostatic system is Defects in primary hemostasis

Easy bruising, petechiae (small dots), purpura (bleeding into the skin), ecchymoses (large superficial hemorrhaging), and spontaneous bleeding, especially from mucosal surfaces

Defects in secondary hemostasis Prolonged deep bleeding into joints/muscles or hematomas:

With these disorders can see spontaneous bleeding (severe factor deficiency) or post-injury (mild factor deficiency)

Combination Multiple site bleeding occurs in severe combined defects

(DIC). Platelet activity and coag proteins are related so disorders of one can affect the other since platelets provide phospholipid binding sites for clotting factor interaction.

A: PetechiaeB: EcchymosisC: Hematoma

EVALUATION OF POTENTIAL BLEEDING DISORDER Obtain Medical history

Age of onset Symptoms Family history Drug history Exposure to toxins

Physical exam Type and sites of bleeding Spontaneous/ result of trauma

Order and interpret lab screening tests Platelet count PT PTT BT or PFA

VASCULAR SYSTEM DISORDERS

Defects may be due to abnormalities in the endothelial cell lining of the blood vessel(acquired) or the connective tissue supporting the vessels(hereditary)

Symptoms Superficial bleeding Hemostatic testing is normal

VASCULAR DISORDERS

Inherited Rare Bleeding and easy bruising are common

symptoms Conditions

Marfan syndrome Ehlers-Danlos syndrome

VASCULAR DISORDERS: ACQUIRED

Patient exhibits bruising and petechiae In all acquired disorders, the patient exhibits

purpura.

Defects in vasculature is caused by: Conditions that decrease the supportive

connective tissue in the blood vessel walls Presence of abnormal proteins in the vascular

tissues Infections or allergic conditions Mechanical stress

VASCULAR DISORDERS: ACQUIRED

ClassificationPurpura due to decreased connective tissue

Collagen and elastin fibers, which form the support for blood vessels, are lost, causing fragilitySenile purpura( elderly people)Scurvy ( deficiency of vitamin C)

Purpura associated with paraprotein disordersPurpura due to vasculitis

Inflammation of small blood vessels due to complement activation on subendothelium

drugs and infectious agents

PLATELET DISORDERS

Platelet disorders are the most common cause of abnormal bleeding. Qualitative: abnormalities of platelet

functionQuantitative: platelet count is below or

above reference rangeHallmarks

PetechiaeExcess bleeding from superficial sites

Mucous membranes, skin

PLATELET ABNORMALITIES Agranular platelet

Giant platelet

QUANTITATIVE DISORDERS- ITS ALL ABOUT THE NUMBERS..

Thrombocytopenia Decrease in the number of circulating platelets-

below 100,000/µL Most common cause of clinical important

bleeding Symptom of underlying disease Bleeding time is prolonged PT, PTT not affected

QUANTITATIVE DISORDERS: THROMBOCYTOPENIA

1. Increased destruction : bone marrow function is normal

Immune Mediated Destruction Immune Thrombocytopenic Purpura (ITP): Caused by antibodies that cover the platelets

Acute and chronic forms Resulting from an unknown cause (Idiopathic)

Often follows a viral infection Believed to be antibody mediated, may produce a

specific platelet autoantibody, specifically IgG. Spontaneous remission occurs in approximately

80% of the cases

Alloimmune Thrombocytopenia Alloantibodies stimulated by foreign antigens cause

destruction

ACUTE VS. CHRONIC ITP

Acute ITP Chronic ITP

Predominantly in children, following viral illness

Adults aged 20-50 yearsIdiopathic

Sudden onsetLasts les than 6 months

Insidious onsetLasts more than 6 months

Platelet counts <20,000/µL

Platelet counts 30,000/µL-80,000/µL

Petechiae, ecchymoses, mucosal bleeding

Mucosal bleeding, easy bruising, petechiae

Affects both sexes equally Prevalence in females

QUANTITATIVE DISORDERS: THROMBOCYTOPENIA (CON’T)

Drugs HIT: Heparin Induced Thrombocytopenia

Heparin causes platelets to activate which eventually causes antibodies to target the heparin/PF4 complex

Results in thrombocytopenia

Other Diseases Collagen disorders

LE, RA Infections

Infectious MononucleosisHIV

QUANTITATIVE DISORDERS: THROMBOCYTOPENIA

Nonimmune: excessive consumption Platelets are activated without the

cascade activating TTP: Thrombotic Thrombocytopenic

Purpura DIC: Disseminated intravascular

coagulation HUS: Hemolytic uremic syndrome Mechanical destruction by artificial heart

valves

QUANTITATIVE DISORDERS: THROMBOCYTOPENIA

2. Decreased production : bone marrow is abnormal bone marrow impairment, radiation, malignancy,

drugs, congenital conditions3. Abnormal distribution sequestering by the spleen or liver3. Excessive dilution transfusions of stored blood or plasma expanders3. Conditions with multiple mechanisms of

thrombocytopenia Example: Alcoholism: Patients that have cirrhosis

present, can have problems with the coagulation proteins as well as their platelets. Alcohol reduces platelet numbers and causes defects of aggregation, release and procoagulant activity. Platelet production is suppressed by the toxic effect of alcohol on the bone marrow.

QUANTITATIVE DISORDERS Thrombocytosis

Temporary rise in the number of circulating platelets Plateletshave normal function. Counts > 1000 x 103/mL

Primary thrombocytosis: uncontrolled production of megakaryocytes CML Polycythemia vera Essential thrombocythemia

Secondary or reactive thrombocytosis: due to another disease or condition Surgery, particularly splenectomy ( since spleen

normally contains 20-30% of the platelets Inflammation Acute blood loss Exercise

ESSENTIAL THROMBOCYTHEMIA

Clonal disorder Results in very high platelet counts (> 1 million) Results in variable-sized platelets

Seen in middle-aged population, both men and women

Clinical signs Hemorrhage Platelet dysfunction Thrombosis

QUALITATIVE DISORDERS: FUNCTIONAL

Manifestations include: Petechiae Easy and spontaneous bleeding from mucous

membranes Prolonged bleeding from trauma

Lab Diagnosis Platelet count is normal to slightly decreased Prolonged bleeding time PT, PTT, Fibrinolysis tests are normal Platelet aggregation studies variable

INHERITED DISORDERS OF PLATELET FUNCTION

Disorders of adhesion Defects in platelet-vessel wall interaction

Disorders of aggregation Defects in platelet-platelet interaction

Disorders of platelet secretion and abnormalities of granules

Disorders of platelet secretion and signal transduction

Disorders of platelet coagulant-protein interaction

QUALITATIVE (FUNCTIONAL) DISORDERS: INHERITED

Disorders of Platelet Adhesion: platelet to vessel wall interaction Bernard-Soulier syndrome

Deficiency of a membrane glycoprotein (GPIb/IX) Giant platelets with coarse granulation and vacules

may be seen. Platelet adhesion, aggregation and bleeding time/ PFA-

100 are abnormal No treatment available, only supportive measures

Von Willebrand’s disease Deficiency of the von Willebrand factor(vWF) OR

production of a dysfunctional protein Abnormal platelet adhesion and bleeding time/PFA-100

as well as abnormal PTT ( due to VIII defect)

Bernard-Soulier syndrome

@2007 Rector and Visitors of the University of VirginiaCharles E. Hess, M.D and Lindsey Krstic, B.A.

QUALITATIVE (FUNCTIONAL) DISORDERS: INHERITED

Disorders of Platelet Aggregation: platelet to platelet interaction Glanzmann’s thrombasthenia

Deficiency of thrombasthenin Lack the GPIIb/IIIa complex, which is where fibrinogen

attaches to platelet surface Abnormal platelet aggregation, clot retraction and

bleeding time Absence of Fibrinogen

QUALITATIVE (FUNCTIONAL) DISORDERS: INHERITED Disorders of Platelet Secretion, Abnormalities of

granules and Signal transduction Deficiencies of Dense Granules

Storage pool disease Platelets appear normal on peripheral smear, but

there is a decrease or absence of dense granules Platelet aggregation abnormal

Deficiencies of Alpha Granules Gray Platelet Syndrome

Agranular platelets Defective Thromboxane A2 Synthesis

Platelet secretion and aggregation affected Defects in Signal transduction

Affects platelet to agonist interactions

QUALITATIVE (FUNCTIONAL) DISORDERS: INHERITED

Disorders of Platelet Procoagulant Activity Scott syndrome Activated platelets secrete and aggregate

normally but fail to bind coagulation factors

INHERITED PLATELET DISORDERS

Disorder Defective Platelet Component

Platelet Count

BT/PFA-100 Other

Bernard- Soulier Syndrome

Glycoprotein Ib/IX

Normal or decreased

Increased Giant platelets

Glanzman thrombasthenia

Glycoprotein IIb/IIIa

Normal Increased

Storage pool disease

Dense granule deficiency

Normal Increased

Gray Platelet syndrome

Alpha granule deficiency

Decreased Variable Agranular platelets

Defective thromboxane A2 synthesis

Deficiency of cyclooxygenase, or TXA2 synthase

Normal Increased

QUALITATIVE DISORDERS: ACQUIRED Uremia

Presence of toxin or waste products affects action of platelets

Liver Disease/Alcohol Reduction in clotting proteins, platelets

Hematologic Disorders Myeloproliferative Disorders, Acute leukemias,

myelodysplasia, multiple myeloma and macroglobulinemia

Drugs Aspirin: prevents the release of thromboxane A2, thus

decreasing platelet secretion. Those platelets affected by aspirin still circulate but are nonfunctional

Antibiotics: penicillins & cephalosporins. Drug coats the platelet membrane blocking ADP and epinephrine receptors, so platelet can not respond to agonist.

SCREENING TESTS OF PRIMARY HEMOSTASIS

Platelet Count

PT aPTT Template BT

Vascular Disorders

Normal Normal Normal Normal or abnormal

Thrombocytopenia

Decreased Normal Normal Abnormal

Platelet Dysfunction

Usually normal

Normal Normal Normal or abnormal

VASCULAR DAMAGE

REFERENCES

@2007 Rector and Visitors of the University of Virginia Charles E. Hess, M.D and Lindsey Krstic, B.A

Castellone, D. D. (2010, October). Complexities of Immune Platelet Disorders. Advance for Administrators of the Laboratory, 19(10), 27-30.

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