1. Transfusion reactions
- seconds to minutes -anaphylaxis. Anti IgA. Use washed RBC next time
- minutes in someone on ACEI - transfusion hypotension from bradykinin in the blood, which is usually broken down by ace
- within the first hour - hemolysis from ABO incompatibility. F/c, Flank pain, hemoglobinuria => renal failure, DIC
- minutes to hours - bacterial sepsis from contamination (pseudomonas can grow in the cold) - sepsis, shock, DIC
- within the first six hours it's either TRALI (donor anti-leukocyte reaction => pulmonary edema and interstitial infiltrates on CXR) or febrile Non-hemolytic Transfusion reaction (from stored cytokines in the blood). Prevent both with leukoreduced pRBC.
- 24 hours to two weeks - delayed hemolysis due to minor antigens
- Occurs after two weeks - transfusion associated GVHD. Donor leukocytes engraft and replicate, and then attack the skin causing rashes, the liver causing hepatitis, the G.I. tract causing mucositis and diarrhea, and the bone marrow causing pancytopenia. Death rate is nearly 100% without a bone marrow transplant. Prevent with irradiated RBC.
2. Preparations for pRBC
- Leukoreduction: reduce white cell component of packed RBC. Prevents non-hemolytic transfusion febrile reactions because it stops the accumulation of cytokines from remnant white cells. It also stops the transmission of CMV so it's good for patients who are CMV negative who you really don't want to get CMV, such as AIDS patients, people awaiting transplant or status post transplant. Leukoreduction is also good for preventing HLA sensitization and thus is good for people who are going to need chronic transfusions.
- Washing the cells will remove any plasma antibodies. This is especially good for people are IgA deficient and will have anaphylactic reaction to IgA in transfused blood.
- Irradiating blood causes cross-linking of DNA which prevents replication of transfused leukocytes. This is to prevent TA-GVHD. Someone with a a normal number of functional T-cells will be able to destroy the transfused white cells. But people with congenital T cell immune deficiencies (such as Wiskott-Aldrich, SCID), bone marrow transplant recipients, premature infants and fetuses, can't. Also people receiving transfusions from close relatives - because the HLA is similar enough that the recipient T cells will not recognize the donor cells as foreign.
3. Microangiopathic Hemolytic Anemia (MAHA): In all causes, the mechanism is the formation of a fibrin mesh due to increased activation of coagulation. The red blood cells are physically cut by these protein networks => schistocytes.
- Valves: Rapid acceleration, fragmentation, and collision jets were associated with high shear stress and hemolysis whereas slow deceleration and free jets were not.
- Malignant HTN: The characteristic vascular lesion is fibrinoid necrosis of arterioles and small arteries, which causes the clinical manifestations of end-organ damage. Red blood cells are damaged as they flow through vessels obstructed by fibrin deposition, resulting in MAHA.
- TTP: <5% ADAMTS-13 activity + presence of ADAMTS13 inhibitor + clinical symptoms of an acute thrombocytopenia and evidence of MAHA, appropriately defines a diagnosis of TTP. Because the sensitivity of ADAMTS-13 deficiency it is not well established, a deficiency of the protein alone does not constitute a diagnosis of TTP.
- TTP + pregnancy: The association of pregnancy with TTP may account for some of the hypercoagulable risk in women near term and postpartum. In a large study of TTP cases, 10% of all cases were diagnosed during pregnancy or postpartum, with the majority of episodes occurring near delivery.
- HUS: kids < 4-5 years, prodrome of bloody diarrhea caused by shiga-toxin producing EHEC (0157:H7). 5-10% with 0157:H7 present with acute HUS. Thrombocytopenia, MAHA, and renal failue. The toxin binds glycolipid surface receptor on endothelial cells under the influence of inflammatory cytokines => platelet clumping.
- HELLP: preeclampsia + MAHA + thrombocytopenia. Usually resolves within days following delivery. The risk of TTP in subsequent pregnancies is hard to determine.
4. TTP & Drugs: quinine (common), mitomycin, penicillin, oral contraceptives, and anti-platelet agents (ticlopidine and clopidogrel)
- Mechanism: either antibody vs drug => immune destruction or direct side effect.
- Make quinine-dependent platelet antibodies => make antibodies to multiple target tissues, which result in the systemic involvement seen in TTP.
- Mitomycin: dose-related effect, causes MAHA and thrombocytopenia. Onset may be sudden due to the initial toxicity or may appear gradually due to the cumulative toxicity of the drug. Most patients in this category responded well to plasma exchange.
- Ticlopidine and clopidogrel: deficiency of ADAMTS-13 and an inhibitor of ADAMTS-13 activity has been noted. Most respond to plasma exchange.
5. Lesser known hemoglobinopathies:
- Hb S-B-thal: When you make all Hb S and no Hb B-thal (called sickle cell-beta zero thalassemia), it's almost identical to sickle cell disease. When you make some B-thal (called sickle cell-beta plus thalassemia), the condition is less severe.
- HB lepore: similar to beta-thalassemia (electrophoresis and smear); decreased hemoglobin synthesis. Homozygous Hb Lepore is rare. Patients of Balkan descent have the most severe presentation of - severe anemia during the first five years of life + significant splenomegaly, hepatomegaly, and skeletal abnormalities similar to homozygous beta-thalassemia. The amount of Hb Lepore in the patients blood ranged from 8 to 30%, the remainder being fetal hemoglobin (Hb F). Homozygous Hb Lepore is similar to beta-thalassemia major, however the clinical course is variable. Patients with this condition typically present with severe anemia during the first two years of life. The heterozygote form is mildly anemic (Hb 11-13 g/dl) but presents with a significant hypochromia and microcytosis.
6. Electrophoresis vs HPLC :
- Electrophoresis allows the simultaneous study of about 90 samples on a single plate, using a central cathode and two anodes. At a glance, any band with abnormal mobility is detected as well as the absence of the normal Hb A band. This method is considered as a first line test and requires a confirmation by a second one, usually CE-HPLC.
- HPLC allows quantitative detection of Hb S and of the most common Hb variants
7. Fluid where there shouldn't be fluid:
- Valves: Rapid acceleration, fragmentation, and collision jets were associated with high shear stress and hemolysis whereas slow deceleration and free jets were not.
- Malignant HTN: The characteristic vascular lesion is fibrinoid necrosis of arterioles and small arteries, which causes the clinical manifestations of end-organ damage. Red blood cells are damaged as they flow through vessels obstructed by fibrin deposition, resulting in MAHA.
- TTP: <5% ADAMTS-13 activity + presence of ADAMTS13 inhibitor + clinical symptoms of an acute thrombocytopenia and evidence of MAHA, appropriately defines a diagnosis of TTP. Because the sensitivity of ADAMTS-13 deficiency it is not well established, a deficiency of the protein alone does not constitute a diagnosis of TTP.
- TTP + pregnancy: The association of pregnancy with TTP may account for some of the hypercoagulable risk in women near term and postpartum. In a large study of TTP cases, 10% of all cases were diagnosed during pregnancy or postpartum, with the majority of episodes occurring near delivery.
- HUS: kids < 4-5 years, prodrome of bloody diarrhea caused by shiga-toxin producing EHEC (0157:H7). 5-10% with 0157:H7 present with acute HUS. Thrombocytopenia, MAHA, and renal failue. The toxin binds glycolipid surface receptor on endothelial cells under the influence of inflammatory cytokines => platelet clumping.
- HELLP: preeclampsia + MAHA + thrombocytopenia. Usually resolves within days following delivery. The risk of TTP in subsequent pregnancies is hard to determine.
4. TTP & Drugs: quinine (common), mitomycin, penicillin, oral contraceptives, and anti-platelet agents (ticlopidine and clopidogrel)
- Mechanism: either antibody vs drug => immune destruction or direct side effect.
- Make quinine-dependent platelet antibodies => make antibodies to multiple target tissues, which result in the systemic involvement seen in TTP.
- Mitomycin: dose-related effect, causes MAHA and thrombocytopenia. Onset may be sudden due to the initial toxicity or may appear gradually due to the cumulative toxicity of the drug. Most patients in this category responded well to plasma exchange.
- Ticlopidine and clopidogrel: deficiency of ADAMTS-13 and an inhibitor of ADAMTS-13 activity has been noted. Most respond to plasma exchange.
5. Lesser known hemoglobinopathies:
- Hb S-B-thal: When you make all Hb S and no Hb B-thal (called sickle cell-beta zero thalassemia), it's almost identical to sickle cell disease. When you make some B-thal (called sickle cell-beta plus thalassemia), the condition is less severe.
- HB lepore: similar to beta-thalassemia (electrophoresis and smear); decreased hemoglobin synthesis. Homozygous Hb Lepore is rare. Patients of Balkan descent have the most severe presentation of - severe anemia during the first five years of life + significant splenomegaly, hepatomegaly, and skeletal abnormalities similar to homozygous beta-thalassemia. The amount of Hb Lepore in the patients blood ranged from 8 to 30%, the remainder being fetal hemoglobin (Hb F). Homozygous Hb Lepore is similar to beta-thalassemia major, however the clinical course is variable. Patients with this condition typically present with severe anemia during the first two years of life. The heterozygote form is mildly anemic (Hb 11-13 g/dl) but presents with a significant hypochromia and microcytosis.
6. Electrophoresis vs HPLC :
- Electrophoresis allows the simultaneous study of about 90 samples on a single plate, using a central cathode and two anodes. At a glance, any band with abnormal mobility is detected as well as the absence of the normal Hb A band. This method is considered as a first line test and requires a confirmation by a second one, usually CE-HPLC.
- HPLC allows quantitative detection of Hb S and of the most common Hb variants
7. Fluid where there shouldn't be fluid:
- Lymphocytic pleural effusion - think granulomatous disease such as TB or sarcoid, lymphomas or RA
- Hepatic hydrothorax: typically R sided, manage first with diuretics and salt restricted diet, if that fails consider TIPS if the synthetic function is holding, and there are no contraindications. If TIPS is contraindicated consider pleurodesis.
- Pathophysiology of Baker's cyst: Inflamed synovium produces excess synovial fluid which overflows into the popliteal burs => cyst. If the cyst bursts it can release it's fluid contents into the calf causing an appearance like a DVT; sometimes with crescent-shaped bruise over malleolus. These cysts are associated with RA, OA, and cartilage tears
- Hepatic hydrothorax: typically R sided, manage first with diuretics and salt restricted diet, if that fails consider TIPS if the synthetic function is holding, and there are no contraindications. If TIPS is contraindicated consider pleurodesis.
- Pathophysiology of Baker's cyst: Inflamed synovium produces excess synovial fluid which overflows into the popliteal burs => cyst. If the cyst bursts it can release it's fluid contents into the calf causing an appearance like a DVT; sometimes with crescent-shaped bruise over malleolus. These cysts are associated with RA, OA, and cartilage tears
8. Transplant & Rheum drugs:
- Methotrexate: Inhibits Folic acid usage and thus will affect rapidly dividing cells. It will cause G.I. disturbances like nausea/mucositis, alopecia, toxicities of the liver, macrocytic anemia and sometimes pancytopenia, interstitial lung disease, rash
- Hydroxychloroquine can cause visual disturbances, trigger G6PD, and cause G.I. disturbances
- Cyclosporine : Calcinurin inhibitor = will take down T cells - increases viral infections and lymphoma and can cause kidney damage. Also causes hyperplasia of gingiva + hirsuitism, hyperkalemia, hypertension (2/2 kidney effects), GI effects, increases risk of squamous cell carcinoma.
- Azathioprine: toxic to the pancreas, liver, and bone marrow
- Prograf/Tacrolimus: hits your kidneys hard, narrow therapeutic window. Doesn't cause gingival hyperplasia or hirsuitism, like cyclosporine. Can also hit liver, heart. Also causes hyperkalemia and hypertension.
- Prograf/Tacrolimus: hits your kidneys hard, narrow therapeutic window. Doesn't cause gingival hyperplasia or hirsuitism, like cyclosporine. Can also hit liver, heart. Also causes hyperkalemia and hypertension.
9. Trousseau syndrome: migratory thrombophlebitis, seen in pancreatic, lung, prostate, colon, stomach cancer and acute leukemias. The tumors release mucins that react with platelets to form microthrombi.
10. Infectious endocarditis
- Vascular manifestations: systemic thrombi to brain, spleen, or kidney, septic emboli to lungs, spleen. conjunctival hemorrhages, mycotic aneurysms, Janeway lesions (erythematous macules on palms and soles)
- Immune manifestations: arthritis, positive RF, glomerulonephritis (dark and cloudy urine 2/2 hematuria and proteinurea, Osler's notes (painful violaceous lesions on the fingers and toes), Roth spots (retinal hemorrhages)
- Specialized bacteria and their sources: Eikenella from oral cavity, strep bovis from occult colon cancer, enterococcus from complicated UTI, staph aureus from contaminated needles
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