Hematology Flashcards
Reticulocyte count
1st step up in work-up in any anemia. Young RBC. Takes 24h -> mature one (biconcave). If low/inappropriate response, bone marrow problem. If high, not bone marrow problem b/c responding well. Takes 5-7 days for reticulocyte response.
Correct the reticulocyte count for the degree of anemia?
Corrected = HCT/45 * reticulocyte count. 3% or greater = good response
Reticulocyte
Still synthesizing Hgb. Black lines are RNA filament (w/ stain). POLYCHROMASIA (basophilic) = means that bone marrow is really responding and bringing out even younger cells. These cells take 2-3 days to mature. We don’t want polychromasia cells in our corrected reticulocyte count. DIVIDE by two if see polychromasia.
Rule of 3
Multiply hgb x 3 ~ HCT. BTW, transfusion of pRBC. For every unit of pRBC transfuse - hgb by 1 and HCT by 3%.
Fe deficiency anemia
Most common cause is GI bleed.
MCV
Mean corpuscular volume. MCV < 80 is microcytic. MCV > 100 is macrocytic (usu. B12 or folate). But what if dimorphic population, then MCV looks normal but you are not normal (RDW increased).
Fe, Folate, B12 absorption where?
Duodenum, jejunum, terminal ileum
RDW
Reports size distribution. Anemia doesn’t happen immediately. Developing microcytic anemia will give you a low MCV with higher RDW. Low MCV and higher RDW = Fe-deficiency. Can’t be thalassemia b/c genetic and congenital.
Spherocyte
Too little membrane. Spherocyte is an Anorexic cell. NO central pallor.
Target cell
Too MUCH membrane. Obese cell right in the middle more membrane and more hgb to be red. Markers for Alcoholics (Chol conc.) and hemoglobinopathy (thalassemia, sickle cell)
Microcytic anemia
GREATER area of pallor b/c less hgb.
Physical signs of anemia
Spoon nails (iron deficiency, koilonychia), cheilosis, pallor of conjunctiva, Lead line
Iron studies
4 studies: Serum Fe (100); Ferritin - soluble, circulating form of iron storage = iron stored in bone marrow; transferrin = carrying protein for Fe made in the liver;
Transferrin and TIBC
ARE THE SAME.
Fe storage and transferrin are related
When the Fe stores are deficient, signal for liver to make more TRANSFERRIN. TIBC increases in Fe-deficiency.
% Saturation
= Serum Fe / TIBC. Normal is 100/300 = 0.33.
Pathogenesis of microcytic anemia
Can’t make Hgb. Hb concentration in developing red blood cell that determines the # of cell division. If Hb is LOW, increases the number of mitoses. All 4 microcytic anemias have LOW Hb.
What makes hemoglobin is how you think of microcytic anemia?
Heme = Fe + protoporphyrin. HbA1 = alpha + beta. Alpha + Delta = A2. Alpha + gamma = Fetal.
Fe-deficiency anemia
No Fe to make Heme. Low hgb. Microcytic.
Anemia of chronic disease
Response to inflammation. Bacteria likes Fe, so decrease Fe availability. Fe is usually in MACROPHAGES in bone marrow. Lock away the Fe but lose the key. Serum Fe low. TIBC is LOW (high iron stores = dec. transferrin). %Sat = low. Serum ferritin = high.
Sideroblastic anemias
Sidero = Iron. Porphyrin synthesis begins in the mitochondria. 3 main causes: (1) EtOH (not the most common anemia in alcoholics) b/c it’s a mitochondrial poison that uncouples oxidative phosphorylation. Fe filled in mitochondria = RINGED sideroblast. And iron overload disease. (2) B6 deficiency (e.g. INH treatment) - no B6, no ALA-synthase. Fe can’t get out of mitochondria again = ringed sideroblast (3) Lead poisoning - lead denatures proteins, esp. FERROkelotase > ala dehydratase. And, again, Fe gets stuck in mitochondria.
Porphyrin synthesis
Succinyl-CoA + Glycine (btw inhibited by tetatnospasmin) -(ALA-synthase; pyridoxine)-> delta-aminolALA ->->->-(in mito)->protoporphyrin + Fe -(Ferrokelotase)-> Heme. Feedbacks against ALA-synthase.
Thalassemias
Genetic diseases AR.
Hb electrophoresis
HbA is 95%. HbA2 is 1-2%. HbF is 1%. PERCENTAGES.
Alpha-thalassemia
AR. Asian, Blacks. Problem in making alpha-globin chains. ALL hemoglobins are EQUALLY decreased. DOESNT show up on electrophoresis. 4 alpha-chain synthesis genes. Deletion of 1 = normal. 2 dels = minimal decrease; mild anemia; microcytic b/c the globin production is decreased (alpha-thalassemia minor). 3 dels = large decrease; 4 beta chains come together to make Hb H. (will show up on electrophoresis; Hb H disease). 4 dels = spontaneous abortion (usually). 4 Gammas = Hb Barts. In Asia, more spontaneous abortions -> more choriocarcinomas. Tx = NOT give Fe.
Beta-thalassemia
AR. Blacks, Greek, Italians. Beta chain decreased. B by itself = normal. B+ = not making a lot. B0= not making at all. SPLICING, STOP codons (most severe = Cooley’s anemia). Alpha, delta, gamma, okay. HbA DECREASES, HbA2 and HbF increase. WILL be on Hb electrophoresis. Tx = transfusion if most severe (but will die of Fe-overload).
Beta-delta thalassemia
Blacks. Only alpha and gammas are left. Hereditary Hb F disease. NO problems.
Causes of Fe-deficiency anemia
Prematurity = loses iron when NOT in utero. Preemies need Fe. Newborn = blood in stool (most of it usually mom’s). [e.g. bleeding Meckel’s diverticulum]. Woman < 50 = menorrhagia. Woman < 20 = anovulatory cycles. Men < 50: peptic ulcer disease. Men and women > 50: Colon Cancer. Fe low. TIBC is HIGH. %Sat = Fe/TIBC = LOW. Serum ferritin is low.
Fe studies in mild thalassemias
NORMAL
Ringed sideroblast
Prussian Blue in bone marrow. Not in smear.
Lead poisoning
“Coarse basophilic stippling.” B/c lead denatures ribonuclease -> persist ribosomes. VERY specific. On X-ray, deposits in epiphysis (failure to grow). Severe, abdominal colic, cerebral edema (increased vessel permeability and buildup of delta-ALA acid!) -> convulsion. Paint, cars, moonshine from radiators, pottery painter. Neuropathies.
Sideroblastic lab studies
Fe-overload (like hemochromatosis). Fe high. Fe stores are high. Transferrin/TIBC LOW. %Sat high. Ferritin high.
B12 and folate in DNA synthesis
dTMP. Not be able to mature the nucleus -> large cells (any of the nucleated cells - squamous, GI, etc.). Megaloblastic anemia.
B12 = cobalamin
B12 has cobalt.
Methyltetrahydrafolate
Circulating folate. B12 takes a methyl off of MTHF. THF and methylcobalamin. W/o B12, can’t get methyl off –> dec. DNA synthesis
Methylcobalamin does what?
Homocysteine + CH3 = methionine. Done by methylcobalamin. Methionine is used for 1C transfer reactions.
If you’re B12 or folate deficiency?
Homocysteine should be HIGH b/c it can’t be turned into methionine. Homocysteine produces thromboses 2/2 endothelial dmg. Folate deficiency is most common reason for high homocysteine.
Tetrahydrafolate
Thymidylate synthase makes dTMP.
Dihydrolate reductase
DHF -> THF. MTX, TMP, pyrimethamine.
Odd-chain fatty acid metabolism
B12 is involved with propionate metabolism. Cofactor for methylmalonyl CoA -> succinyl CoA (involved with myelin synthesis?). Methylmalonic acid is a very specific and sensitive test for B12 deficiency. Neurologic manifestations of B12 deficiency is due to build-up of FA metabolites -> myelin can’t be synthesized -> demyelination of lateral corticespinal and dorsal columns..
Normal metabolism of B12
Animal product. Pure vegetarians NEED B12 supplementation. Binds to R factor in saliva. Protect it from destruction by acid. Intrinsic factor made by parietal cells in the body-fundus. IF isn’t destroyed by acid. B12-R goes into duodenum where intrinsic factor around. R factor cleaved (requires Pancreas). B12 binds intrinsic factor –> terminal ileum -> receptors for intrinsic factor. (Same place where bile salts, Crohn’s disease). B12 has 6-9 yr supply
Etios of B12 deficiency
Most common is pernicious anemia. Destruction against parietal cells + other cells around = ATROPHIC gastritis. Achlorhidia -> predispose for gastric adenocarcinoma. Chronic alcoholics b/c of pancreatitis and can’t cleave R factor. Pure veg. Some tapeworm eats B12. Bacterial overgrowth (2/2 peristalsis problem; diverticular). Terminal ileal disease (aka Crohn’s). Will see hypersegmented neutrophil.
Folate
Animal AND plant products. In a polyglutamate form. Can’t be absorbed in jejunum. Enzyme converts (intestinal conjugase) turns it into mono-form. (Phenytoin blocks intestinal conjugase -> macrocytic anemia). Monoglutamate at jejunum. Two things prevent this absorption: (1) OCP (2) Alcohol. Main reason why alcoholics are folate deficient. Folate has 3-4 months supply. Hypersegmented neutrophils.
Why the anemia in B12/folate deficiency?
Cords of Bilroth in spleen. Fixed macrophages where RBC’s are caught. In BM, cells have to fit through small holes to get through sinusoids. Megaloblastic cells (b/c of DNA problems) have a HARD time getting out. Macrophages eat up the cells. Therefore, pancytopenia.
Schilling’s test
Test for localizing B12 deficiency. The cause. Give radioactive B12 by mouth. Urine 24h. If nothing came out, NO absorption of B12. NOW: Radioactive B12 + IF = urine + means pernicious anemia. If neg, 10-day broad spectrum. Try radioactive, if + in urine = bacterial overgrowth. If NEG, NOW get pancreatic extract + radioactive B12 = urine + means chronic pancreatitis. If Not, Crohn’s, tapeworm.
Normocytic anemias w/ low reticu count
Some etios - early Fe-deficiency and anemia of chronic disease. Still need to get a Ferritin (will detect before anemic). Etio - blood loss < 1 week. No reticulocyte up b/c it takes 5-7 days for BM to rev up. Etio - aplastic anemia = No Bone Marrow. Pancytopenia. Idiopathic. Etio - decreased EPO 2/2 chronic renal failure. Etio - malignancy
Etios of aplastic anemia
Drugs - chloramphenicol, indomethacin, phenylbutozone, thyroid drugs. Infections - HEPATITIS C, Parvovirus (if only RBC). Radiation.
Mechanisms of hemolysis
Two ways: Intravascular or Extravascular (outside of blood vessels). Extravascular = macrophage (usu. cords of Billroth in Spleen) kills IgG, C3b, out-of-shape, Howell-Jolley [tries to take it out and often kill the cell]. Autoimmune (IgG, C3b), Sickle cell disease. End product of phagocytosed RBC = unconjugated bilirubin –> lipid-soluble unconjugatrd bilirubin and binds to albumin and goes to the liver. Therefore, extravascular hemolytic anemias have jaundice. NONE of that bill gets into the urine (b/c albumin and lipid-soluble)
Intravascular hemolysis
Die within the vessel. Congenital bicuspid valve. IgM-mediated on surface of RBC -> all the way to C9 = MAC = hole. Releases hemoglobin. Haptoglobin is the Hb binder = complex that is phagocytosed by macrophage in order to retrieve the hemoglobin and don’t lose it. Haptoglobin decreases. Usually don’t get jaundice. Hemoglobunuria + Haptoglobin low.
Intrinsic vs. Extrinsic Hemolytics Anemia
Intrinsic = something wrong with RBC (spectrin, decay-accelerating factor to neutralize complement, sickle cell, G6PD, PNH); Extrinsic = nothing wrong with RBC (microangiopathic/macroangiopathic anemias; autoimmune hemolytic anemia)
Intrinsic hemolytic anemia
Reticulocyte count > 3%. MAD = Membrane-defect (spherocytosis, PNH), Abnormal Hgb (Sickle cell trait/disease), Deficient enzyme (G6PD def.)
Hereditary Spherocytosis
Removed extravascularly = jaundice (unconjugated). Spectrin. AD. Splenomegaly. Gall bladder disease 2/2 to Ca bilirubinate (pigment?) stones. Dx = osmotic fragility test. Tx = splenectomy
Paroxysmal Nocturnal Hemoglobinuria
Defect in DAF (Decay-accelerating factor). During sleep, mild resp. acidosis -> predisposes to complement attaching to cells (platelets, RBCs, WBCs). DAF -> inc. degradation of complement. Intravascular hemolysis. Morning urine red. Pancytopenia.
Sickle cell disease
AR. Sickle cells on smear. Trait will only have sickle cells in renal medulla and peritubular capillaries. 60%+ HbS in RBC —> sickling. Lowered O2 tension can induce sickling. Hemolytic anemia (extravascular) + occlusion of small blood vessels by sickled cells (vaso-occlusive crisis). Damaged organs over time (nonfunctional by age 2 [Howell-Jolley Body, Strep. pneumo sepsis] and autosplenectomy by 2nd decade). But can’t give Pneumovax till age 2. Newborns have HbF 70% and can inhibit sickling. By 6-9 mo, 1st crisis. Dactilytis. BONE infarction. Susceptible to osteomyelitis by SALMONELLA. Spleen. Hydroxyurea inc. HbF synthesis.
G6PD Deficiency
X-linked recessive (other enzyme X-linked = Lesch-Nyhan). G6P is used to make glutathione, ribose, glycogen. RBC’s don’t have catalase so rely on glutathione to get rid of peroxides. HEINZ bodies (hgb clumped up). Damages membranes -> mostly intravascular hemolysis. Precipitated by infections, drugs (primaquine, dapsone [leprosy]), fava beans. Black, mediterranean. BITE cells. Dx = Don’t use enzyme assays during hemolysis b/c only get bad enzyme. Confirm with a G6PD assay AFTER hemolytic episode.
Autoimmune hemolytic anemias
Warm = IgG. Cold = IgM. Most common is WARM and is SLE. IgG and C3b on surface of RBCs -> extravascular hemolytic anemia. Coomb’s Test (Direct, IgG, C3b for RBC) is POS. (Indirect Coomb’s is often used to screen pregnant women for ab’s).
Three types of drug-induced hemolytic anemia
Penicillin: BPO group attaches to red blood cell. IgG antibody develops against group (HS type II). Methyl-dopa (anti-HTN for pregnant women [hydralazine - drug-induced lupus and methyldopa]): alters Rh antigens -> autoAb’s against own Rh antigens. Immune-complex: Quinidine is classic. Acts as a haptan and a IgM attaches to drug = Immune-complex. (HS-3). Intravascular hemolysis via MAC -> hemoglobinuria and decreased Haptoglobin.
Microangiopathic hemolytic anemia
Schistocytes. AS is most common cause. Intravascular - low haptoglobin. Hemoglobinuria. Could also get Fe-deficiency anemia. Other causes = DIC, TTP, HUS 2/2 PLT plug damages, runner’s anemia, malaria. Falciparum (ring forms, multiple, any time fever)
Benign changes on cells
Leukomoid reaction: looks like leukemia but is benign. 2/2 TB, sepsis. >50k cells in the blood. Over-exagerrated response to infection = kids. Pertussis has WBC > 60k (scary b/c ?ALL).
Atypical lymphocyte
Large bluish cells. CMV, EBV, toxoplasmosis, any hepatitis, phenytoin. EBV infects B cell at CD21. [6-8 week contact sports. splenic rupture]
Monospot?
Heterophile antibodies. e.g. Anti-HORSE, anti-sheep Ab’s in the blood! Look for horse RBC’s to agglutinate in person’s serum.
Monocyte
King of CHRONIC inflammation. Will see monocytosis in RA. Crohn’s. Lupus. Malignancy.
Eosinophilia
Hay fever, PCN allergy, ONLY invasive helminths (pinworms are NOT invasive). No protozoa.
Polycythemia
Increased RBC count, Hg, HCT. RBC mass vs. count? Mass is total # in body (mL/kg of body weight). Count = RBC/microliter of blood. Count is high in volume depletion. Two types: relative and absolute. Relative is decreased plasma volume. (Most common cause).
Absolute polycythemia
Appropriate or inappropriate? Appropriate? If there is a cause of tissue hypoxia. Inappropriate? No tissue hypoxia. Polycythemia vera (JAK2) - neoplastic disease of stem cells. EPO-producing tumor/cyst.
Myeloproliferative disease
Stem cell disease where the stem cell has lost regulation:. Polycythemia vera, CML, fibrous tissue replacement, essential thrombocythemia, MDS.
Polycythemia Vera
4 H’s = Hyperviscosity (inc. peripheral resistance -> thrombosis, Budd-Chiari), Hypervolemia (increase in plasma volume that matches RBC mass, only one of polycythemias), Histaminemia (mast cells and basophils; after a shower -> itch all over the body! 2/2 temp changes), Hyperurecemia (all the purines from the dying nucleated cells like neutrophils). Tx - Phlebotomy - lower viscosity, make them Fe-deficient. RBC mass inc, Plasma vol inc, O2sat normal, EPO is LOW.
Leukemia general characteristics
Malignancy of stem cells in the marrow that can metastasize anywhere. Generalized lymphadenopathy, hepatosplenomegaly. Abnormal cells in the peripheral blood - blasts (myelo, lymph, mono, megakaryo). Crowd out normal hematopoietic cells = normocytic anemia. USU. thrombocytopenia too. Usu. increased in WBC b/c of the abnormal cells. Acute vs. chronic. Blasts < 30% qualifies as CHRONIC. Blasts >30% is ACUTE. Age-brackets are key
0-14 y/o
ALL
15-39 y/o
AML. Auer rods.
40-59 y/o
AML and CML.
> 60
CLL (also most common leukemia overall, most common cause of generalized non-tender lymphadenopathy b/c of metastases)
CML dx proof
Philadelphia chromosome. 9;22. BCR-ABL. Stain - leukocyte alkaline phosphatase (mature neutrophils had this stain. immature one’s do not. Look for LACK of staining). Leukocyte alkaline phosphate score is LOW.
Primary Myelofibrosis; Agnogenic myeloid dysplasia
Extramedullary hematopoiesis (usu. spleen) and fibrosis in the bone marrow. Dictator said let’s move to the spleen. However, some people stay in the BM. Worm their way through strands of fibrous tissue = Teardrop cells.
Essential thrombocythemia
too many platelets
Acute lymphoblastic leukemia
Common ALL Antigen B-cell Leukemia (CALLA Ag = CD10+).
Chronic lymphoblastic leukemia
Smudge cell. Hypogammaglobunemia 2/2 inability to differentiate into plasma cells. Most common cause of death = infection. Generalized non-tender lymphadenopathy.
Hairy Cell Leukemia
TRAP stain. Tartrate-resistant acid phosphatase stain.
Acute myelogenous leukemia
Auer rods = abnormal lysosomes. Infiltrates gums = acute monocytic leukemia. Acute promyelocytic leukemia - DIC, LOTS of auer rods, t(15;17), tx with retinoic acid -> maturing blasts to mature into benign cells.
Painful LN
NOT malignant. B/c it’s inflammatory -> pain.
Non-tender LN
Think malignant. Metastases. Then primary lymphoma.
Generalized LN
Systemic disease. Painful - inflammatory (e.g. HIV, EBV, SLE)
Histiocytosis X
Problem would be in the sinuses of LN’s.
Follicular lymphoma
Most common non-Hodgkin’s. t(14;18). Overexpression of BCL-2 (anti-apoptosis)
What tissues are resistant to tissue invasion?
Cartilage and elastic tissue
Mycosis fungoides
Helper T-cell. Usu. involves skin (plaques). Sezary cell = malignant T-cells in the blood
Hodgkin’s disease
Localized non-tender lymphadenopathy, night sweats, fevers. Reed-Sternberg cell are the malignant cell. Owl-eye. Even though are a lot of other cells. Prognosis ~ amount of Reed-Sternberg. Most common type Nodular Sclerosing - Woman. Nodes in anterior mediastium + one ABOVE the diaphragm (neck, supraclavicular)
SPEP
Albumin migrates the furthest b/c it has most negative charge. Polyclonal vs. monoclonal. Polyclonal = many clones of B-cells. GAMMA = IgG > IgA > IgM. Chronic inflammation increased IgG -> polyclonal gammopathy = benign. Monoclonal gammopathy = ONE clone of Plasma cells are making immunoglobulin = usually malignancy of plasma cells. Often times light chains are made = Bence-Jones protein in Urine.
Multiple myeloma
>
- Incurable except bone marrow. Igkappa most common type. Plasma cells = IL-1 (osteoclast activating factor) —> lytic lesions are SHARP. Pathologic fractures (e.g. rib fracture. Plasma cells have sheets of RER on EM (b/c making LOTS of proteins).
Amyloid
Many different proteins are transformed into it. e.g. pre-albumin, calcitonin, light chains (MM), APP. BETA-amyloid is toxic to neurons.
Wrinkled cytoplasm macrophage
Gaucher cell.
Bubbly cytoplasm macrophage
Niemann-Pick disease
What prevents thrombosis in our small blood vessels - arterioles, venules, capillaries?
Heparin - glycosaminoglycan, a mucopolysaccharide; enhances antithrombin III (made in the liver). PGI2 (prostacyclin) - made by endothelial cells; vasodilator; Protein C & S (vitamin K dependent) - they cleave V, VIII (Ochocinco). Antithrombin can’t take out V, VIII b/c they aren’t serine proteases. t-PA activates plasminogen -> plasmin -> eats fibrin clot.
OCP thrombogenic?
Makes V, VIII. Inhibits AT-III.
Bleeding time
Evaluates PLT function. Nothing to do with coagulation factors. Volar aspect of forearm, 1 mm wound, stopwatch. Every 30 s dab wound. When No blood, stop. 7-9 min.
Cut vessel
Release tissue thromboplastin. Activates extrinsic factor factor. Expose collagen -> XIIa is activated (intrinsic factor). vWF (made by endothelial cells and MEGAkaryocyte in BM) is exposed. PLT’s have GIb receptor -> release of ADP and Ca2+. ADP is an aggregating agent for PLT via GpIIb/IIIa and fibrinogen. PLT makes TXA2 (PLT is only cell that can make TXA2 via thromboxane synthesis) -> vasoconstrictor, PLT aggregator, bronchoconstrictor). Blocks up open lumen (PLT plug - temporary hemostatic; held together by fibrinogen).
Mast cell
IgE bridged by Ag -> immediate degranulation of histamine, serotonin, eosinophil chemotactic reaction. Then it releases arachidonic acid to make prostaglandins and leukotrienes (30-1h later) -> enhancing the HS-1 reaction.
Prolonged bleeding time?
Thrombocytopenia, von willebrand’s disease (AD - 1/250), ASA (most common cause - blocks PLT cyclooxygenase; irreversible), other NSAIDs (reversible in 48 hrs)
Now what with our PLT plug?
TF + XII are activated. Thrombin converts fibrinogen -> fibrin. Plug is PLT with fibrinogen. Now thrombin will make plug STABLE that isn’t dislodged. Plasminogen -> plasmin will re-canalize.
Coagulation defect vs. platelet deficiency
PLT deficiency has prolonged BT. Small vessels will bleed easily. Petechiae. Ecchymoses or purpura. Epistaxis. Coagulation deficiency: normal bleeding time. LATE re-bleeding problems - initially okay, but move around and all your temporary plugs get dislodged. Often seen in wisdom tooth removal. Menorrhagia, GI bleed, and hemoarthroses also seen more in coagulation deficiency.
Platelet abnormality tests
PLT count. Bleeding time tests platelet function. vWF test = ristocetin co-factor assay (DEC. agglutination)
Reverse ASA-induced. Man with OA in surgery bleeding to death with all cog’s normal and plt count normal.
Platelet-pack transfusion?
Extrinsic system
Factor VII.
Intrinsic system
Factors XII, XI, IX, VIII.
Common final pathway
X, V, II, I (fibrinogen)
PT
EXTRINSIC.
If PTT prolonged and PT normal what is it most likely wrong?
Most likely VIII (Hemophilia A).
Warfarin’s effects on coagulation.
- Usu. follow PT. PTT will also be prolonged. But PT does a better job following warfarin b/c more factors.
Heparin follow what?
Follows PTT. XII, XI, VII, X, Prothrombin, thrombin affected by antithrombin III. PTT better at evaluating heparin. But PT is prolonged too.
Fibrinolytic system
Plasmin breaks down fibrinogen and fibrin, coagulation factors. Fragments are fibrin-degradation products. BEST test for DIC is D-Dimer. Fibrin stabilizing factor = XIII. D-dimers ONLY detects those fibers that have a link. THAT MEANS THERE WAS A FIBRIN CLOT! (D-dimers also seen in thrombosis in PE, STEMI + checks to see if re-canalized after t-PA).
Senile purpura
Vessels get unstable. SQ tissue thins. Ruptured vessels. Only in places that hit things - back of hands, shins.
Hereditaory telangiectasia = osler weber rendu
Many telangiectasias around skin, GI.
Petechia vs. spider angioma?
Spider angioma WILL BLANCH b/c it’s an AV fistula. Petechia does NOT blanch.
Autoimmune thrombocytopenic purpura
HS-2 Ab against PLT (GpIIb/IIIa). Macrophages in spleen remove.
TTP and HUS
Not DIC. Not consuming coagulation factors (no PTT, PT changes). Something in plasma damages small vessels -> PLT sticks and aggregates and form firm platelet plugs in ALL small vessels in the body = consuming all the platelets. Thrombocytopenia. Bleeding -> Schistocytes (diagnostic). Renal failure. HUS caused by O157:87 E coli (beef) toxin damages the vessels.
Hemophilia A vs. von Willebrand disease
Von willebrand’s disease = PLT adhesion defect + Factor VIII (mild) deficiency -> plt and coagulation defects (epistaxis, easy bruising, menorrhagia). VIII antigen - carries vWF and VIII around in the blood. Hemophilia A = X-recessive. vWF = AD. Hemophilia A only has VIII deficiency. Tx = DDAVP (desmopressin) causes synthesis of all factor VIII muscles (vWF, VIII, VIII ag) used for vWF and mild Hemophilia A. ESTROGEN also increases all these factors (OCP’s help)
Diagnosis of vWF?
Need to use ristocetin co-factor assay. PTT and bleeding time is not good.
Anti-phospholipid syndrome
Includes “lupus anticoagulant” + anti-cardiolipin antibodies. Both cause vessel thrombosis. Anti-cardiolipin can make VDRL or RPR positive b/c uses beef cardiolipin.
DIC
Disseminated Intravascular Coagulation. Forming clots throughout the body in small vessels. Consumes fibrinogen, V, VIII, prothrombin, platelets. Thrombi + anti-coagulated b/c only have serum NOT plasma. Hemorrhagic thrombosis syndrome. Etiology = septic shock (e.g. E. coli), snake bite (e.g. rattlesnake), ARDS, thromboplastin in amniotic fluid embolism. Clinically, bleeding from EVERY orifice = mouth, GI, venipuncture, etc. Labs - PT, PTT prolonged. PLT down. D-Dimers positive [test of choice].
Hereditary thrombosis
Young person with a DVT.
Factor V Leiden
Abnormal factor V that Protein C and S CANNOT break down. Thrombogenic.
Anti-thrombin III deficiency
Etio - most commonly OCP’s. Clinical scenario - give heparin to patient and PTT DOES NOT prolong.
Blood group O
Anti-AB IgG, Anti-A IgM, Anti-B IgM
Blood group A
Anti-B IgM
Blood group B
Anti-A IgM
Blood group AB
No antibodies.
Newborn blood
Has NOOOO anti-X ab’s for blood groups b/c they don’t synthesize IgM until they are BORN. After 2-3 months, make IgG.
Old people blood
Hardly any antibodies. More tolerant of transfusion of non-matched blood.
Gastric cancer association?
Blood group A
Duodenal ulcer association
Blood group O
Rh factor
There are 5 Rh antigens. Positive for just ONE (Rh-D).
Duffy Ag
Missing in BLACK population. Not as likely to get Plasmodium vivax b/c P. vivax needs duffy ag to get into RBC.
Anemias protecting against malaria
P. falciparum protection. RBC lives too short and falciparum can’t live out its entire life-splan.
Major cross match?
Patient serum in test tube + blood of the donor unit. Looking for anything in serum that will attack blood?
Ab screen
Is an INDIRECT Coombs.
Developing Ab’s to blood transfusion
The more units of blood you get, the more likely you will develop antibodies against blood. Over time, it is harder to find blood that will cross-match to your blood if you receive too many transfusions.
HIV screen in blood bank
ELISA - anti-gp120 Ab. Western blot looks for 3-4 ab’s for specificity.
What is most common infection transmitted by blood transfusion?
CMV
What is most common cause of post-transfusion hepatitis?
Hep C
How do you prevent a newborn getting a transfusion from getting CMV or graft v host?
Irradiate blood to kill lymphocytes. CMV also lives in lymphocytes
Accidental needlestick - most common infection?
HBV
Needlestick from HIV+ patient?
1/300. Tx = 2 RTI + PI x 6 months w/ screens
Basic rule for when to transfuse?
When you’re symptomatic
FFP
Shouldn’t be used to expand plasma volume. You use NS instead. Use it for multiple coagulation factor deficiencies like DIC, warfarin overdose, cirrhosis and bleeding.
Allergic transfusion reaction
Itching, hives. Potentially anaphylaxis. HS-1. Plasma in donor gives allergen. Tx = diphenhydramine + antihistamine
Febrile transfusion reaction
HLA-Ab’s against leukocytes from donor unit -> release of pyrogens = fever. ONLY if someone has been transfused before (e.g. women who were pregnant).
Hemolytic transfusion reaction
Very rare. Go into shock immediately b/c IgM are quick to complement activation (wrong blood). Occasionally, major cross match isn’t perfect. Memory B-cell’s can react but there are no Ab’s b/c the transfusion was too long ago. This reaction takes time (hrs-week) -> IgG antibodies. “Delayed hemolytic transfusion reaction.” Test to get = Coomb’s test.
ABO incompatibility
Blood group O women. Anti-AB IgG in bloodstream that can cross -> attack blood cell of fetus. No clinical problems in utero b/c of mom’s liver. After birth, immediate jaundice b/c baby’s liver can’t handle all the unconjugative bilirubin on its own. Physiological jaundice is at DAY 3. Very mild hemolytic anemia. Coomb’s test on baby’s cells = +. ANY pregnancy.
UVB light
Converts bilirubin -> a dipyrole (water-soluble)
Rh incompatibility
Mom is Rh - but baby is Rh +. 1st pregnancy = OK. But a fetal-maternal bleed -> develop antibodies against Rh-D. Next time IgG ab will cross placenta, Rh-D -> bad hemolytic anemia. When baby is born, worse anemia and jaundice then ABO probably requiring exchange transfusion. Prevention: Rh(anti-d) immunoglobulin that can’t cross the placenta. Given at 28 weeks for ppx. During birth, test to see if fetal blood cells in the maternal blood. Amount of maternal-fetal bleed -> more Rho (anti-d). ABO incompatibility PROTECTS against Rh b/c the Anti-IgM’s will destroy all the fetal blood cells quickly.
Erythroblastosis fetalis
Die of heart failure. High-output failure (dec. viscosity 2/2 severe anemia). Extramedullary hematopoiesis.
Kernicterus
Unconjugated hyperbilirirubinemia. Lipid-soluble gets into the lipid-rich brain -> basal ganglia = kernicterus
