Diseases for Final Flashcards
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
Kaposi’s Sarcoma
Rare cancer of blood vessels that is caused by HHV-8.
Associated w/ HIV
Manifests as bluish-red oval-shaped patches that eventually become thickened. Lesions may appear singly or in clusters.
Predictive of disease progression to AIDS
AIDS
When HIV infected patient’s CD4 drops below 200.
At risk of contracting: Pneumocystic jivoreci, cryptococcal meningitis, and toxoplasmosis
If CD4 drops below 50:
- Mycobacterium avium
- CMV
- Lymphoma
- Dementia
- Most deaths occur with Cd4 counts below 50
Other key opportunistics:
-TB, Cryptosporidosis, Isosporiasis, NHL, VZV/HSV encephalitis and skin
Risk factors for death within 3 years:
- CD4 below 200
- Viral load over 100,000
- Older than 50 years of age
- Injection drug user
- Having prior AIDS-defining illness
Pneumocystis jiroveci (carnii)
Most common opportunistic infx in HIV. Interstitial pneumonia.
Yeast-like fungus.
Commonly found in healthy lungs, but rarely causes sx unless immunocompromise.
Dx: sx, CXR, sputum silver stain (induced by bronchioalveolar lavage)
Sx: SOB, dry cough, fever
Rx: Bactrim
