bleeding and thrombotic disorders · bleeding disorders • von willebrand disease • hemophilia a...
TRANSCRIPT
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Bleeding and
Kristine Krafts, M.D.Thrombotic Disorders
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Bleeding disorders• von Willebrand disease• Hemophilia A and B• DIC• TTP/HUS• ITP
Thrombotic disorders• Factor V Leiden
Bleeding and Thrombotic Disorders
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Platelet bleeding
• Superficial (skin)• Petechiae• Spontaneous
Factor bleeding
• Deep (joints)• Big bleeds• Trauma *
* Includes prolonged bleeding after dental work
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Petechiae
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Palatal petechiae
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Palatal ecchymosis
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Purpura
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Bleeding after buttock injection in
patient with hemophilia
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Bleeding disorders• von Willebrand disease
Bleeding and Thrombotic Disorders
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• Most common hereditary bleeding disorder
• Autosomal dominant
• vW factor decreased (or abnormal)
• Variable severity
Things you must know
Von Willebrand Disease
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• Huge multimeric protein
• Made by megs and endothelial cells
• Glues platelets to endothelium
• Carries factor VIII
• Decreased or abnormal in vW disease
What’s von Willebrand Factor?
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TFVIIIX
VIII
fibrin
clot
thrombin
XV
Intrinsic Extrinsic
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• Mucosal bleeding in most patients
• Deep joint bleeding in severe cases
Symptoms of Von Willebrand Disease
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• Bleeding time: prolonged
• PTT: prolonged (�corrects� with mixing study)
• PT: normal
Lab Tests in Von Willebrand Disease
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• DDAVP (raises VIII and vWF levels)
• Cryoprecipitate (contains vWF and VIII)
• Factor VIII
Treatment of Von Willebrand Disease
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Bleeding disorders• von Willebrand disease• Hemophilia A and B
Bleeding and Thrombotic Disorders
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• Most common factor deficiency
• X-linked recessive in most cases (30% are spontaneous mutations)
• Factor VIII level decreased
• Variable amount of “factor” bleeding
Things you must know
Hemophilia A
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TFVIIIX
VIII
fibrin
clot
thrombin
XV
Intrinsic Extrinsic
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Hemophilic arthropathy of knee
Normal knee Knee of patient with hemophilia
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Joint Deformity in Hemophilia
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Lab tests• PTT prolonged• Factor VIII level low• DNA studies abnormal
Treatment• DDAVP • Factor VIII
Hemophilia A
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• Factor IX level decreased
• Much less common than hemophilia A
• Same inheritance pattern
• Same clinical and laboratory findings
Things you must know
Hemophilia B
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TFVIIIX
VIII
fibrin
clot
thrombin
XV
Intrinsic Extrinsic
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Bleeding disorders• von Willebrand disease• Hemophilia A and B• DIC
Bleeding and Thrombotic Disorders
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Thrombosis Hemorrhage
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• Malignancy
• OB complications
• Sepsis
• Trauma
Remember these for sure:
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Bleeding disorders• von Willebrand disease• Hemophilia A and B• DIC• TTP/HUS
Bleeding and Thrombotic Disorders
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• Pentad: MAHA, thrombocytopenia, fever, neurologic defects, renal failure
• Deficiency of ADAMTS13
• Big vWF multimers trap platelets
• Plasmapheresis or plasma infusions
Things you must know
Thrombotic Thrombocytopenic Purpura
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Rodent of unusual size (ROUS)
-The Princess Bride, 1987
Von Willebrand multimer of unusual size (MOUS)
- NEJM, 1982
Nasty creatures
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Clinical pentad• Hematuria/jaundice (MAHA)• Bleeding/bruising (thrombocytopenia)• Fever• Bizarre behavior (thrombi in CNS)• Renal failure (thrombi in kidney)
Treatment• Plasmapheresis (in acquired TTP) • Plasma infusions (in hereditary TTP)
Thrombotic Thrombocytopenic Purpura
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• MAHA and thrombocytopenia
• Most are related to E. coli infection
• Toxin damages endothelium
• Treat supportively
Things you must know
Hemolytic Uremic Syndrome
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Bleeding disorders• von Willebrand disease• Hemophilia A and B• DIC• TTP/HUS• ITP
Bleeding and Thrombotic Disorders
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• Antiplatelet antibodies coat platelets
• Splenic macrophages eat platelets
• Diagnosis of exclusion
• Steroids or splenectomy
Things you must know
Idiopathic Thrombocytopenic Purpura
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Bleeding disorders• von Willebrand disease• Hemophilia A and B• DIC• TTP/HUS• ITP
Thrombotic disorders• Factor V Leiden
Bleeding and Thrombotic Disorders
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Endothelial damage• Atherosclerosis
Stasis• Immobilization• Varicose veins• Cardiac dysfunction
Hypercoagulability• Surgery• Carcinoma• Estrogen/postpartum• Thrombotic disoders
Thrombosis Risk Factors
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• no obvious cause• family history• weird location• recurrent• patient is young• miscarriages
When should you worry about a hereditary disorder?
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• Most common cause of unexplained thromboses
• Inherited point mutation in factor V gene• Factor V can’t be turned off
• High risk of thrombosis if homozygous
Things you must know
Factor V Leiden
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What is Factor V Leiden?
A mutated factor V gene• Single point mutation• Discovered in Leiden, Netherlands
Produces abnormal factor V• Participates in the cascade• Can’t be cleaved by protein C
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You can turn it on…
…but you can’t turn it off !
Yeah, so?
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TFVIIIX
VIII
fibrin
clot
thrombin
XVa
Intrinsic Extrinsic
V
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TFVIIIX
VIIIa
fibrin
clot
thrombin
XVa
Intrinsic Extrinsic
proteinC
V
VIII
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Factor V Leiden
Diagnosis• PTT and INR not helpful• Need genetic testing
Treatment• Don’t! Unless there is a thrombosis.• Then give oral anticoagulants