Aspen Falls Lifestyle P RESENTED BY M ARIA M ARTINEZ, C ITY M ANAGER.
MLAB 1227- C OAGULATION K ERI B ROPHY -M ARTINEZ Coagulation Disorders: Primary Hemostasis.
Transcript of MLAB 1227- C OAGULATION K ERI B ROPHY -M ARTINEZ Coagulation 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.
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
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
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.
http://image.bloodline.net/stories/storyReader$618