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HbESE Asians (not Chinese or Japanese) / microcytosis, hypochromia / may have target cells on peripheral smear but no clinically significant anemia Thalassemias Epidemiology: Mediterranean, SE Asia, Africa Mechanism: low supply of one chain(s) results in buildup of remaining chains / hypochromic/microcytic (normal RDW, uniform size) / severe forms lead to extramedullary hematopoeisis, splenomegaly, hypersplenism, folate deficiency and perhaps megaloblastic anemia, hyperuricemia Diagnosis: hemoglobin electrophoresis / totally iron levels usually normal Treatment: transfusions (see below for each subtype) A α2β2 normal Hb F α2y2 fetal Hb A2 α2d2 microcytic anemia marker - ↑ in β-thalassemia, ↓ in Fe deficient anemia H β4 α -thalassemias / forms Heinz bodies / causes hemolysis Bart’s y4 α -thalassemias in fetus/infants
Bo thalassemia (major)no B chains / only survive (until puberty) if they also inherit persistent HbF B+ thalassemia (B+ severe / B+ negro) increased HbA2, except in dB thalassemia / MCV < 80 heterozygotes thalassemia minor homozygotes thalassemia major (B+ negro homozygotes have thalassemia intermedia) α -thalassemia (each haplotype codes for 2 alpha chains, which do not cross over) (a-) α -thalassemia-2 gene (--) α -thalassemia-1 gene (a-/aa) 20% African Americans / lessens severity of HbS (a-/a-) or a-thalassemia trait / microcytic, slightly hypochromic / no significant anemia (--/a-) causes HbH buildup and minor to major thalassemia (--/--) causes severe anemia, CHF in utero leads to hydrops fetalis
Transfusion Medicine FFP, cryoprecipitate, IVIG, platelets, factor VIII Blood transfusions Indications: Hgb 7g/dL usually enough (except in cardiovascular disease where Hct > 30 desired) Labs: expect rise in Hct 3% for each unit of PRBC’s (300cc; 250 mg iron) Risk of infections: HCV: 1 in 103,000 / HTLV I, II, HIV: 1 in 700,000 / HBV: 1 in 66,000 / B19 Bacterial contamination rare, parasites ruled out by screening questions Adverse reactions (see hemolytic anemia) Overall rare of occurrence: 1-4% ABO incompatibility Presentation: hypotension, hemoglobinuria, chills, fever, flank pain Treatment: stop transfusion, may even need dialysis to remove Ab complexes Milder, delayed hemolytic reactions Febrile non-hemolytic reactions (range from minor to major) Treatment (mild): Tylenol, Benadryl Treatment (severe): similar to hemolytic anemia TRALI: transfusion related lung injury (can mimic aspiration pneumonia; can cause severe pulmonary edema requiring mechanical ventilation) / caused by antibodies in donor blood against HLA on host WBCs Platelet transfusion Each unit increases platelet count by 5 to 10,000/mm3 Indications: < 50,0000 with bleeding or < 10,000
Precipitated FFP fibrinogen, some clotting factors / less volume than FFP Intravenous Immune Globulin (IVIG) Uses: ITP, hemolytic anemia, premature babies, autoimmune neutropenia, burn victims, leukemia, myeloma / works faster than other agents / can be useful for refractory autoimmune diseases including dermatomyositis, ITP, SLE, has been used in TSST (S. aureus), many more indications IV infusion over ~5 days / given in 3 month cycles? / very expensive / made from pooling many samples (watch out for BSE) Dosage: 400 mg/kg for 5 days (high-dose 1 g/kg over 5 days for acute chronic ITP) Note: avoid in patients with IgA deficiency (can get anaphylaxis from preformed Ab’s) Side effects: often causes aseptic meningitis (~bad headache lasting 24-48 hrs, give Tylenol before IVIG) Factor VIIa (recombinant) Being studied for use in acute ICH to limit expansion of hemorrhage (optimal guidelines being worked out 1/07) Factor VIII Highly purified form may not have enough vWF in it to treat vWD Thrombocytopenia [Ddx] HIT, TTP, ITP, APA, DIC ITP (Idiopathic Thrombocytopenic Purpura) [NEJM] General: platelet destruction by RES / NO splenomegaly / occurs more in women 20-40 yrs / 85% acute, 15% chronic / harbinger of SLE Childhood: acute post-viral event (weeks later, IgG mediated), may last up to 6 months because IgG is distributed throughout all ECM (33% of body water) / chronic ITP of childhood similar to chronic ITP of adulthood Labs: normal clotting time, prolonged bleeding time / Ab unhelpful because of many false positives Ddx: other causes of thrombocytopenia Treatment: IVIG works fast, may last for weeks (give when platelets < 10,000) prednisone 1-2 mg/kg platelet transfusion often consumed immediately splenectomy and immunosuppressants are last resort Prognosis: children 3-6 months then resolves spontaneously Adult insidious, subacute to acute / uncommon spontaneous remission
Incidence: 1-5% of heparin exposees Early (type I): day 2 to 3, usu. not severe, not mediated by IgG Late (type II): one week, antibodies that aggregate platelets in presence of heparin (bind to complex of platelet factor 4 and heparin), can persist for 6 wks, causes thrombosis / formation of antibodies influenced by type of heparin, dose, and circumstance (2% baseline, 15% ortho patients, 50% CABG patients) / only some HIT-patients become thrombocytopenic Note: risk of thrombosis (white-clot syndrome) is higher than risk of bleeding at 5-10% per day even first few days after heparin discontinued (including patients w/ HIT and normal platelet counts) / mean platelet drop to 60,000 / only 5% drop to < 15,000 Findings: red/necrotic lesions at sites of SC injection, decreased platelets by 30% Labs: check HIT Ab’s or PF4 antibodies (takes several days to come back; high sensitivity but this test only has moderate specificity—because there can be anti-PF4 antibodies which are not clinically pro-thrombotic) Treatment: avoid heparin (including heparin flushes), avoid warfarin and ancrod (during the acute phase) because they may exacerbate prothrombotic state / if thrombosis present or other indication for anticoagulation, must use lepirudin or argatroban (direct thrombin inhibitors) or possibly danaproid and/or long-term warfarin / thrombolysis, thrombectomy, IVIG, plasmapheresis, antiplatelet agents as indicated Coagulation (see hypercoagulability) [diagram of clotting cascade] [thrombin] Pro-coagulants Initiating pathway (extrinsic) PT – defective VII (tissue factor) has clinical bleeding Maintenance pathway (intrinsic) aPTT – defective VIII, IX, XI have clinical bleeding Defective V, X, prothrombin/thrombin – both PT and aPTT are increased All sorts of cells secrete tissue factor (stimulated by Il-1B) Binds 7a and then 10 – forms 10a (inhibited by LMWH) Regulated V and VIII is important (they act as scaffolds for reactions) Anti-coagulants Plasminogen to plasmin, which competes with thrombin for the same sites on the clot Thrombin-thrombomodulin-nice closed loop with protein C, which inactivates V and VIII Inhibitors – can sometimes be diluted 400/500 fold with normal plasma and still prevent clotting Protein C and Protein S – regulate coagulation Antithrombin III (stimulated by heparin) – inactivates IIa and Xa TFPI acts at Xa to prevent unnecessary coagulation Liver disease (II, VII, IX, X) early liver/warfarin/vitamin K deficiency: PT rises before PTT because factor VII has shorter half-life (although that doesn’t make sense to me looking at the diagram) Prolonged Thrombin Time inhibitors of thrombin heparin, fibrin degradation products (FDP) elevated in DIC / also elevated in renal failure, liver disease (see D-dimer) low fibrinogen abnormal fibrinogen - late liver disease, inherited Other tests: Fibrinogen decreased in DIC – other conditions D-dimer is most specific test for DIC Bleeding time (unreliable due to poor technicians) Starts increasing at < 100,000 Platelet aggregometry Secretion tests Prothrombin consumption test
Note: epistaxis should last less than 5 minutes (recurrent epistaxis may be benign) Hemophilia A XLR / 1 in 10,000 males / bleeding into soft-tissue, muscle, weight bearing joints / bleeding usu. occurs when levels < 5% / may occur hours or days after trauma / may involve any organ / elevated aPTT Treatment: factor VIII levels must reach 25-50% to control bleeding into joints / half-life of factor VIII only 8-12 hrs / must be given twice daily as FFP, cryo (contains ½ factor VIII activity of FFP in one tenth the volume / DDAVP (causes release of vWF from tissue and may help in very mild cases) / purified factor VIII or Humate-P (for severe cases; may be needed for weeks) Factor VIII inhibitor can be acquired (post-transfusions) or idiopathic/autoimmune Treatment: prothrombinase complexes, porcine factor VIII (may resist the anti-VIII antibodies), treat with factor VIII transfusions, factor VIIa (activates factor X), immunosuppression (steroids, chemotherapy, rituximab), human recombinant factor VIII (can give but will get used up quickly)
may not be adequately replaced with purified factor VIII (should give product mixtures instead) DDAVP (causes release of stored vWF; usu. adequate for treatment of type I mild disease; won’t help Type III) estrogen/progesterone increase primary and constitutive secretion of vWF (increased 50% during pregnancy) Osler-Weber-Rendu [dermis] AD inheritance with incomplete penetrance / endoglin Presentation: epistaxis, skin telangiectasias, visceral AVMs / continuous bruit in systole and diastole / high-output cardiac failure
Lungs: ~
Liver: hepatomegaly, hepatic encephalopathy, cirrhosis of HHT Kidneys: hematuria Diagnosis: contrast echocardiography, ABG, IV digital subtraction / MRI/angiography of brain and lungs (more sensitive than CT), CBC (r/o anemia) Treatment: surgical correction of AVM’s Re-check patients every 5-10 yrs / children must be re-examined after puberty / screen relatives Factor XII – Christmas disease? generally not clinically significant Hypercoagulability [diagram of clotting cascade] [prevalence chart] Congenital: Factor V Leiden > prothrombin G20210A, hyperhomocysteinuria, dysfibrinogenemia Acquired: malignancy (Trousseau’s), myeloproliferative, PNH, CTD (SLE), Behçet’s, Buerger’s Vasculitis, PRV, primary thrombocythemia, TTP, DIC, DM Congenital or Acquired: APA syndrome, protein C deficiency, protein S deficiency, antithrombin deficiency III Work-up: for unexplained DVT/PE, you might start with a PCR for factor V and prothrombin mutation, presence of LA and cardiolipin Ab and check functional assay for protein C, S, ATIII Treatment: current thinking is 1 year full anticoagulation / PREVENT study supports lifelong low-dose coumadin (INR 1.5 to 2.0) (study included most types of hypercoagulable patients except not APAS) [NEJM] APC resistance (Factor V Leiden) most common cause (25%) of 1st idiopathic DVT / whites >> blacks, Asian / 20x risk for homozygotes (7x risk for heterozygotes) / 3-4% incidence of gene in general population / worsened by contraceptives Genetics: mutated factor V APC cleavage site (Arg 506 Glu 506)
most common cause of recurrent DVT / increased plasma prothrombin / venous/arterial thrombosis Labs: PCR / this test can be done while pt is on heparin/coumadin Treatment: heparin + 3 months coumadin and lifelong anticoagulation Download 3.95 Mb. Share with your friends:
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