bleeding disorders · university of jordan school of medicine •when injury occurs, three...
TRANSCRIPT
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Bleeding Disorders
Ahmad Mansour, MD
University of Jordan
School of Medicine
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• When injury occurs, three mechanisms occur
– Blood vessels
– Primary hemostasis
– Secondary hemostasis
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• Diseases of the blood vessels
• Platelet disorders
– Thrombocytopenia
– Functional disorders
• Clotting factor deficiency
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Let’s talk about some tests
• Platelet count (150,000-450,000)
– Does not mean bleeding will occur if slightly decreased
• Platelet function:
– Bleeding time: old and outdated
– PFA
– Aggregation studies
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• PT: prothrombin time: Extrinsic and common pathways
• PTT: Partial thromboplastin time: intrinsic and common pathways
• D dimer and fibrin split products
– Sensitive for DIC but not specific
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Two major clinical types of bleeding
• Mucocutaneous seen in disorders of the vessels and platelets
– Petechiae and ecchymosis
• Deep bleeding in muscles and joints seen in clotting factor deficiency
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Disorders related to blood vessels
• Increased vascular fragility
• Endothelial damage
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Increased vascular fragility
• Vitamin C deficiency
• Amyloidosis
• Chronic steroid use
• Vasculitis
• Normal platelet count, function, PT and PTT
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• Endothelial damage
– DIC
– overwhelming damage to the endothelial cells converting them to prothrombotic surfaces
• Consumption of platelets and coagulation factors (consumptive coagulopathy)
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DIC
• DIC occurs as a complication of a wide variety of disorders; it is caused by the systemic activation of coagulation and results in the formation of thrombi throughout the microcirculation, consumption of platelets and coagulation factors and severe bleeding
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1- obstetric complication, placental damage
2- cancer: APL and adenocarcinomas
– Releasing proteolytic enzymes
– Releasing tissue factor
3- bacterial sepsis
– Endotoxins trigger release of tissue factors from monocytes
• Monocytes also release IL1 and tumor necrosis factors– Both increase tissue factor and decrease thrombomodulin
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• 4- deposition of antigen-antibody complex such as in SLE
• 5- extremes of temperature
• 6- major trauma such as severe head trauma
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Morphology
• Intravascular hemolysis with schistocytes
• Microthrombi in the small vessels and capillaries
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Clinical manifestations
• Variable
• Could be acute (a in postpartum DIC) or chronic as in cancer
• Can be minimal or severe
– Shock, acute renal failure, dyspnea, cyanosis, convulsions, and coma.
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• Lab findings
– Low platelets
– High PT and PTT
– Elevated FDP
• Prognosis depends on the severity of presentation and the underlying condition
– Treatment with heparin or replacement of coagulation factors
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Thrombocytopenia
• Low platelet count
– Less than 15000
• Bleeding occurs when 20000-50000
– 20000-50000 posttraumatic bleeding
– Less than 5000 spontaneous bleeding
• Mucocutaneous bleeding
– Brain hemorrhage is a major factor for mortality
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• ITP
• HIT
• TTP and HUS
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ITP
• Immune thrombocytopenic purpura
– Acute: children after a viral infection, self-limiting
– Chronic: affects women 20-40 years of age
• Antibodies against platelet antigens (IIb/IIIa and IB/IX)
– Spleen causes damage to those antibody coated platelets
• Benefits of splenectomy
– Steroids, immunosuppressive therapy or splenectomy
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Clinical
• Mucocutaneous bleeding
– Brain hemorrhage is rare
• Lab results
– Low platelets
– Normal PT
– Normal PTT
– Bone marrow shows megakaryocytic hyperplasia
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HIT (heparin induced thrombocytopenia)
• Occurs in 3-5% of patients using unfractionated heparin
– Develops after 1-2 weeks of therapy
– Results in thrombosis associated with low platelets
– IgG antibodies against platelet factor 4 (PF4)
– Cessation of heparin breaks the cycle
– Use of low molecular weight heparin
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TTP and HUS
• THROMBOTIC THROMBOCYTOPENIA PURPURA
• HEMOLYTIC UREMIC SYNDROME
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TTP
• FIVE FINDINGS
– Fever
– Thrombocytopenia
– Microangiopathic hemolytic anemia
– Neurological manifestations
– Renal failure
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HUS
• Fever
• Thrombocytopenia
• Renal failure
• NO neurologic manifestations
• Frequently in children secondary to E. coli infection
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• Both has widespread microthrombi
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So how are they different from DIC???
• No significant consumption of clotting factor
– Normal PT and PTT
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Coagulation disorders
• Hereditary or acquired
• Acquired is more common
– Vitamin K deficiency
• Factors II, VII, IX, and X
• Newborns
• Patients with fat malabsorption such as cystic fibrosis
– Liver disease
– DIC
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• Hereditary
– Von-Willebrand disease
– Hemophilia A
– Hemophilia B
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Von-Willebrand disease
• Autosomal dominant
• Mucocutaneous bleeding
• The most common inherited bleeding disorder
• 1% of the US population
• Frequently asymptomatic and under recognized
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• Labs
– Normal platelet count
– Abnormal platelet aggregation studies
– Elevated PTT
– Normal PT
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Hemophilia A
• Deficiency in factor VIII
• X-linked disorder affects males
• Deep muscle and joint hemorrhage
• Most cases are associated with low factor VIII level
– 10% are associated with normal level but reduced activity
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• Lab results
– Normal platelet count and function
– Normal PT
– Elevated PTT that corrects with mixing studies
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Hemophilia B
• Also called Christmas disease
• Factor IX deficiency
• Deep muscle and joint bleeding (hemarthrosis)
• X-linked disorder
• Affects males
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• Lab results same as hemophilia A
• It is less common than hemophilia A
• Distinguish by doing specific assays for factors VIII, and IX