Diseases for Final Flashcards
(27 cards)
Von Willebrand Disease
Things you must know:
- Most common hereditary bleeding disorder
- Autosomal dominant
- vW factor decreased (or abnormal)
- Variable severity
3 Types of Von Willebrand Disease: Type 1 (70%): Decreased vWF Type 2 (25%) abnormal vWF Type 3 (5%) no vWF
Sx: Mucosal bleeding in most patients (bloody nose, easy bruising, heavy menses), Deep joint bleeding in severe cases.
Lab Tests: Prolonged bleeding time, PTT prolonged (corrects w/ mixing study), INR normal, vWF level decreased (normal in type 2), Platelet aggregation studies abnormal. No agglutination with ristocetin.
vWF - binds GP Ib
Treatment: Desmopressin (DDAVP) (raises VIII and vWF levels in type I), Cryoprecipitate (contains vWF and VIII), Factor VIII prior to procedures
Incidence: 1 in 100 - often asymptomatic however
Hemophilia A
Things you must know:
- Most common factor deficiency
- X-linked recessive in most cases (30% are random)
- Factor VIII level decreased
- Variable amount of “factor” bleeding
Sx: Severity depends on amount of VIII, typical factor bleeding (deep joint, prolonged after dental work), rarely mucosal hemorrhage
Lab tests: INR, TT, platelet count, bleeding time (normal), PTT prolonged (corrects w/ mixing study), abnormal factor VIII assays, abnormal DNA studies
Rx: Desmopressin (DDAVP), Factor VIII (Only when symptomatic)
Hemophilia B
Things you must know:
- Factor IX level decreased
- Much less common than hemophilia A
- X-linked recessive
- Variable amount of “factor” bleeding
Sx: Severity depends on amount of VIII, typical factor bleeding (deep joint, prolonged after dental work), rarely mucosal hemorrhage
Lab tests: INR, TT, platelet count, bleeding time (normal), PTT prolonged (corrects w/ mixing study), abnormal factor VIII assays, abnormal DNA studies
Rx: Desmopressin (DDAVP), Factor VIII (Only when symptomatic)
XI deficiency
Bleeding only after trauma
Rare
XIII deficiency
Severe neonatal bleeding
Rare
Bernard-Soulier Syndrome
Abnormal IB–> abnormal adhesion
Big platelets and severe bleeding
Glanzmann Thrombasthenia
No IIb-IIIa
No aggregation
Severe bleeding
Gray platelet syndrome
No alpha granules
Big empty platelets
Mild bleeding
Delta Granuled Deficiency
No delta granules
Can be a part of Chediak-Higashi syndrome
Disseminated Intravascular Coagulation
Things you must know:
- Underlying disorders
- Something triggers coag, causing many (micro) thrombi
- Platelets and factors get used up, causing bleeding
- Microangiopathic hemolytic anemia.
Causes:
Dumpers - Obstetric comlications, adenocarcinoma, acute promyelocytic (M3) leukemia
Rippers: Bacterial sepsis, trauma, burns, vasculitis.
MOST common: Malignancy Obstetric Complications Sepsis Trauma
Sx: Insidious of fulminant, multi-system disease, thrombosis and/or bleeding.
Labs: INR, PTT, TT, prolonged. FDPs increased, fibrinogen decreased.
Rx: Treat underlying disorder and support with blood products
Idiopathic Thrombocytopenic Purpura
Things you must know:
- Antiplatelet antibodies
- Acute vs. Chronic
- Dx of exlusion
- Steroids or splenectomy
Pathogenesis: Autoantibodies to GPIIB/IIIa or Ib. Bind to platelets. Splenic macrophages eat platelets.
Chronic: Adult women, primary or secondary, insidious (nosebleeds, easy bruising), Danger of bleeding into brain
Acute: Children, abrupt (follows viral illness), usually self-limiting, may become chronic
Labs: Signs of platelet destruction: thrombocytopenia, normal/increased megakaryoctyes, big platelets. INR/PTT, No specific test for ITP
RX: Steroids, IVIG, splenectomy
Thrombotic Thrombocytopenic Purpura
Things you must know:
- Pentad: MAHA, thrombocytopenia, fever, neurologic defects, renal failure
- Defeciency in ADAMTS13
- Big vWF multimers trap platelets
- Plasmapheresis or plasma infusions
Pathogenesis: Just released vWF is unusually large (UL) which causes platelet aggregation, ADAMTS13 cleaves UL vWF into less active bits. TTP is deficient in ADAMTS13
Clinical Findings: Hematuria, jaundice (MAHA), bleeding, bruising (thrombocytopenia), fever, bizarre behavior (neurologic deficits), decreased urine output (renal failure)
Treatment of TTP: Aquired TTP: Plasmapheresis, Hereditary TTP: plasma infusions
Medical emergency as MI from thrombi in coronary arteries is a typical COD.
Hemolytic Uremic Syndrome
Things you must know:
- MAHA and thrombocytopenia
- Epidemic (E. coli) vs. non-epidemic
- Toxin damages endothelium
- Treat supportively (not abx)
Pathogenesis:
Epidemic = E coli O157:H7 makes nasty toxin that injures endothelial cells.
Non-epidemic = defect in complement factor H is inherited or acquired (unsure how this activates platelets)
Clinical findngs:
Epidemic: Children, elderly; bloody diarrhea, then renal failure; fatal in 5% of cases
Non-epidemic: renal failure, relapsing-remitting, fatal in 50% of cases
Treatment: supportive care, dialysis, no abx (increased toxin release)
Thombosis/Emboli
Risk Factors/Virchow’s Triad:
- ) Endothelial damage (atherosclerosis)
- ) Stasis: Immobilization, varicose veins, cardiac dysfucntion
- )Hypercoagulability: trauma/surgery, carcinoma, estrogen/postpartum, thrombotic disorders.
Labs: INR, PTT, TT
Factor V Leiden
Things you must know:
- Most common cause of unexplained thrombosis
- Point mutation in factor V gene (can’t be cleaved by protein C)
- Factor V can’t be turned off
- Need genetic test for dx
Common! Half of patients w/ unexplained thrombosis. 5% of caucasians. VERY rare in non-caucasians
Clot risk: heterozygotes 7x normal; homozygotes 80x normal (normal risk is 1-2 per 1000 per year.)
Dx: PTT and INR are not helpful. Need genetic testing.
Rx: Don’t unless there is a thrombosis. Warfarin as needed.
Antithrombin III deficiency
Things you must know:
- ATIII is a natural anticoagulant (inhibits IIa, VIIa, IXa, XA, and XIa)
- Potentiated by heparin
- Many gene mutations exist, but all are very rare
Clotting risk: homozygotes can’t live; heterozygotes - half get clots;
Rx: antithrombin concentrates required
Protein C and S Deficiencies
Things you must know:
- Proteins C (inactivates Va and VIIIa and S are natural anticoagulants)
- C is also fibrinolytic (promotes t-Pa) and anti-inflammatory (keeps cytokines low)
- Warfarin-induced skin necrosis
- C deficiency rare; S deficiency super rare
Clotting risk: heterozygotes: 7x risk; risk of warfarin-induced skin necrosis and purpura fulminans.
Purpura fulminans
Thombotic state + vascular injury –> skin necrosis.
Associated w/ protein C and S deficiency and sepsis
Rx: protein C
Factor II Gene mutation
Things you must know:
- Factor II = prothrombin
- Mutated gene makes too MUCH prothrombin
- Prothrombin itself is normal
- Caucasians only
5% of caucasians
Clot risk: 2-20x
Hyperhomocysteinemia
Things you must know:
- Homocysteine converts folate
- Homocysteinuria = rare metabolic disorder
- Too much homocysteine = thrombosis
- Many causes.
Not so rare. MTHFR gene mutation or B12/Folate deficiency.
Homocysteine is toxic to endothelium via ROS and interferes w/ NO vasodialation and antithrombotic activity.
Increase risk of thrombis, premature atherosclerosis. Risk of venous thrombosis up 2.5x and arterial thrombosis 10x. (less if secondary to B12 deficiency)
Homocysteinuria
Rare metabolic disorder w/ deficient trans-sulphuration enzyme.
Increase homocystein in blood, urine
Increase thrombosis, premature atherosclerosis
Antiphospholipid Antibody Syndrome
Things you must know:
- Autoantibodies vs. phospholipids
- Falsely prolong INR, syphilis, DAT
- May cause thrombosis
Three variants: anticardiolipin, lupus anticoagulants, antibodies vs. other molecules.
Promote coagulation in vivo; inhibit coagulation in vitro.
Sx: recurrent thrombosis, recurrent abortions, increased risk of stroke, pulmonary hypertension, renal failure
Causes:
Children - infection (mild risk)
Adults - Autoimmune diseases (moderate risk)
Elderly - Drugs (no risk)\
Labs: Prolonged PTT (Doesn’t correct)
Oral Candidiasis (thrush)
Patients w/ HIV/AIDS can present with severe thrush often extending down into esophagus.
Predictive of disease progression to AIDS
Oral Hairy Leukoplakia
OHL is due to epstein-barr virus in immunosuppressed patients. White hairy substance on tongue/mouth.
Predictive of disease progression to AIDS
