Bleeding Disorders - Krafts Flashcards
What are the Hereditary Bleeding Disorders?
von Willebrrand Disease
Hemophilia A and B
Hereditary Platelet Disorder
What are the Acquired Bleeding Disorders?
DIC
ITP
TTP/HUS
What factors are seen when the disorder is due to platelet bleeding?
Superficial (skin)
Petechiae
Spontaneous - no accident
What factors are seen when the disorder is due to factor bleeding?
Deep (joints)
Big Bleeds
Trauma
What are the characteristics of von Willebrand Disease?
Most common hereditary bleeding
Autosomal Dominant
von Willebrand factor decreased
Variable severity
What is the clinical finding of Type 1 Von Willebrand Disease?
Decreased vWF
What is the clinical finding of Type 2 Von Willebrand Disease?
Abnormal vWF
What is the clinical finding of Type 3 Von Willebrand Disease?
No vWF
What is von Willebrand Factor?
Huge multimeric protein made by Megakaryocytes and Endothelial cells
Glues platelets to endothelium
What factor does von Willebrand Factor carry?
Factor VIII (Intrinsic Pathway)
What are the symptoms of von Willebrand Disease?
Most patients are asymptomatic Mucosal bleeding (most) Deep joint bleeding (severe)
What lab tests would be checked and what would the values be in von Willebrand Disease?
Bleeding Time = prolonged PTT = prolonged Mixing Study = corrected INR = Normal vWF level = decreased (except in Type 2) Platelet aggregation = abnormal
What membrane bound proteins are in the platelet?
Phospholipids activate coag factors
GP Ia binds collagen
GP Ib binds vWF
GP IIb-IIIa binds fibrinogen
What makes platelets express the GP Ib membrane bound protein?
Ristocetin (does not work in vWD = missing vWF)
What is the treatment for Von Willebrand Disease?
DDAVP = raises factor VIII and vWF levels
Cryoprecipitate = contains vWF and VIII
Factor VIII
What are the genetic characteristics of Hemophilia inheritance?
X-Linked Recessive Disorder
~30% are random mutations
What are the characteristics of Hemophilia A?
Most common factor deficiency
Factor VIII level decreased
What are the symptoms of Hemophilia A?
Typical “Factor” Bleeding with Deep Joint bleeding or prolonged bleeding after dental work (preceding trauma)
Rarely = Mucosal Hemorrhage or Petechiae
Severity depends on amount of VIII
What lab tests are used to diagnose Hemophilia A and what are the expected values?
Normal: INR, TT, Platelet Count, Bleeding Time
PTT = prolonged
Mixing Study = corrected
Factor VIII assay and DNA studies = abnormal
What is the treatment for Hemophilia A?
DDAVP
Factor VIII
What are the characteristics of Hemophilia B?
Factor IX decreased
Less common than Hemophilia A
X-Linked Recessive Disorder
Same clinical and lab findings
What happens with a factor XI deficiency?
Bleeding only after trauma
What happens with a factor XIII deficiency?
Severe neonatal bleeding
What are the Hereditary Platelet Disorders?
Bernard-Soulier Syndrome
Glanzmann Thrombasthenia
Gray Platelet Syndrome
Delta-Granule Deficiency
What are the characteristics of Bernard-Soulier Syndrome?
Abnormal GP Ib
Abnormal adhesion
Big platelets
Severe bleeding
What are the characteristics for Glanzmann Thrombasthenia?
No GP IIb-IIIa fibrinogen receptor
No aggregation
Severe bleeding
What are the characteristics for Gray Platelet Syndrome?
No alpha granules
Empty, Big platelets
Mild bleeding
What are the characteristics for delta-Granule Deficiency?
No delta granules
Associated with Chediak-Higashi syndrome
What are the characteristics of Disseminated Intravascular Coagulation (DIC)?
Something triggers coagulation causing thrombosis
Platelets and factors get used up causing bleeding
What is the major issue in DIC?
Microangiopathic Hemolytic Anemia
What are the “Dumper” causes of DIC?
Dumper = coagulation substances are dumped into the blood
Obstetric complications
Adenocarcinoma
Acute Promyelocytic Leukemia
What are the “Ripper” causes of DIC?
Ripper = Anything that will damage the endothelium Bacterial Sepsis Trauma Burns Vasculitis
What are the top 4 causes of DIC?
MOST common causes of DIC: Malignancy Obstetric Complications Sepsis Trauma
What are the symptoms of DIC?
Insidious or fulminant
Multi-system disease
Thrombosis and/or Bleeding
What lab tests are used to diagnose DIC and what are the expected values?
Prolonged INR, PTT, TT
Increased FDPs
Decreased Fibrinogen
What is the treatment of DIC?
Treat underlying disorder while supporting with blood products
What are the characteristics of Idiopathic Throbocytopenic Purpura?
Antiplatelet Antibodies
Acute vs. Chronic
Diagnosis of Exclusion
What is the treatment of Idiopathic Thrombocytopenic Purpura?
Steroids (Glucocorticoids)
IVIG
Splenectomy
What is the pathogenesis of Idiopathic Thrombocytopenic Purpura?
Autoantibodies to GP IIb-IIIa or GP Ib
Binds to Platelets
Splenic macrophages eat platelets
What are the characteristics of Chronic Idiopathic Thrombocytopenic Purpura?
Primary or Secondary
Adult Women
Insidious: Nosebleeds, Easy Bruising
DANGER: Bleeding in Brain
What are the characteristics of Acute Idiopathic Thrombocytopenic Purpura?
Children
Abrupt (follows viral illness)
Usually self-limiting
May become chronic
What lab tests are used to diagnose Idiopathic Thrombocytopenic Purpura and what are the expected values?
Normal INR/PTT Signs of platelet destruction: -Thrombocytopenia -Normal/Increased megakaryocytes -Big Platelets
What are some other causes of Throbocytopenia besides ITP?
Aplastic anemia Bone marrow replacement Large spleen Consumptive processes (DIC, TTP, HUS) Drugs
What are the characteristics of Thrombotic Microangiopathies (TTP and HUS)?
Thrombi, Throbocytopenia, AND MAHA
Something triggers Platelet Activation
What are the symptoms of Thrombotic Thrombocytopenic Purpura (TTP)?
MAHA, Thrombocytopenia, Fever, Neurologic Defects, Renal Failure
What is the deficiency associated with TTP?
ADAMTS13
What is the treatment of TTP?
Plasmapheresis (Acquired TTP) Plasma infusions (Hereditary TTP)
What is the pathogenesis of TTP?
Big vWF multimers that trap platelets
What is the normal function of ADAMTS13?
To cleave unusually large vWF into less active bits
What are the clinical findings of TTP?
Hematuria, Jaundice (MAHA) Bleeding, Bruising (Thrombocytopenia) Fever Bizarre Behavior (Neurologic Deficits) Decreased Urine Output (Renal Failure)
What is the most common pathogenesis of Hemolytic Uremic Syndrome (HUS)?
Epidemic usually caused by E. coli toxin-induced injury to endothelial cells
What are the characteristics of HUS?
MAHA and Thrombocytopenia
Toxin that damages endothelium
What is the pathogenesis of Non-Epidemic HUS?
Defect in complement factor H
Inherited or Acquired
What are the clinical findings of Epidemic HUS?
Children/Elderly
Bloody diarrhea, then renal failure
What are the clinical findings of Non-Epidemic HUS?
Renal Failure
Relapsing-Remitting Course
Fatal in 50% of cases
What is the treatment of HUS?
Supportive Care
Dialysis
