Blood Flashcards

Question

Iron deficiency anemia vs. anemia of chronic disease

Answer 1

**Iron deficiency anemia:** - microcytic, hypochromic anemia - low serum ferritin and iron - can be due to loss of blood through GI bleeds **Anemia of chronic disease:** - can be normocytic or microcytic - high serum ferritin - chronic inflammation => increase in cytokines and hepcidin => reduced iron release from macrophages, reduced RBC synthesis from low erthropoietin levels, reduced RBC survival

Answer 2

Occurs in liver and erythroid progenitor cells of bone marrow First and rate-limiting step: **ALA synthase** - glycine + succinyl CoA ⇒ ALA - requires PLP (vit B6) cofactor - regulated via: feedback inhibition (heme/hemin), repression of ALA synthase gene, inhibition of ALA synthase transport from cytosol to mitochondria Last step: **ferrochelatase** - last reaction ⇒ heme - regulated by iron availability in bone marrow

Answer 3

Vitamin B6 deficiency: - Vit B6 (PLP) cofactor is requred for ALA synthase Lead-induced anemia: - lead binds to sulfhydryl groups in ALA dehydratase and ferrochelatase Porphyrias: occur when body has problems making heme 1. AIP: acute intermittent porphyria 2. PCT: porphyria cutanea tarda 3. EPP: erythropoietic protoporphyria

Answer 4

**Pathology:** - defect in **porphobilinogen (PBG) deaminase** (3rd reaction in pathway) - porphobilinogen ==> hydroxymethylbilane **Symptoms:** - neurocognitive: fever, muscle weakness, intellectual disability, limb/head/neck/chest pain - visceral: abdominal pain, vomiting/constipation - second most common porphyria **Labs:** - **PBG** and **5-ALA** accumulate in plasma and urine - urine turns red after being left out **Treatment:** - IV hemin and glucose (negative feedback on ALA synthase) ## Footnote "An Insane Person Peed Blue Dye"

Answer 5

**Pathology:** - deficiency in **uroporphyrinogen decarboxylase (UDC)** (5th reaction) - uroporphyrinogen III ==> coproporphyrinogen III - hepatic - autosomal dominant - precipitated by: alcohol, hepatic iron overload, sunlight exposure **Symptoms:** - photosensitivity due to porphyrin accumulation - light-sensitive blistering, rash, increased hair growth - most common porphyria **Labs:** - **uroporphyrinogen III** accumulates in urine **Treatment:** - sun avoidance, sunscreen - decrease iron load - chloroquine or hydroxychloroquine treat underlying cause ## Footnote "People Can Tell U Drink Constantly"

Answer 6

**Pathology:** - deficiency in **ferrochelatase** (last step) - protoporphyrin IX ==> heme - autosomal dominant **Symptoms:** - hemolytic anemia - extreme photosensitivity w or w/o blistering **Labs:** - accumulation of **protoporphyrin IX** in RBC, plasma, feces (NOT urine) **Treatment:** - physical sun blocks - exchange transfusion - hematin ## Footnote "Easily Produces Pebbly Fingers"

Answer 7

- Neonatal jaundice - Gilberts syndrome - Crigler-Najjar syndrome - Dubin-Johnson syndrome

Answer 8

**Pathology:** - Deficiency in bilirubin glucuronyl-transferase ==> increased unconjugated (indirect) bilirubin - UDP glucuronyl transferase (UGT) activity is low at birth - Rate of bilirubin production is increased due to shorter lifespan of RBCs - Decreased bacteria in intestine ⇒ increased enterohepatic circulation **Symptoms:** - yellow skin - toxic encephalopathy (kernicterus) **Treatment:** - phototherapy with blue light: converts unconjugated bilirubin into water soluble isomer - phenobarbital: induces bilirubin metabolizing enzymes - blood transfusion to prevent brain damage

Answer 9

**Pathology:** - glucuronosyltransferase deficiency - mild increase in unconjugated (indirect) bilirubin **Symptoms:** - generally benign, very mild jaundice during illnesses - 5-10% of population

Answer 10

**Pathology:** - glucuronosyltransferase deficiency - very high unconjugated bilirubin - autosomal recessive **Symptoms:** - profound jaundice - brain damage in infants **Treatment:** - Type I (more severe): phototherapy, liver transplantation - Type II (still severe but less so): phenobarbital to increase expression of UGT1A1

Answer 11

**Pathology:** - mutation in MRP2 gene - autosomal recessive - inability of hepatocytes to secrete conjugated bilirubin out of ER after it's formed ==> mildly increased conjugated bilirubin **Symptoms:** - usually asymptomatic - moderate jaundice

Answer 12

- Bernard-Soulier disease - Glanzmann thrombasthenia - Gray platelet syndrome - idiopathic thrombocytopenia purpura (ITP) - thrombotic thrombocytopenia purpura (TTP)

Answer 13

**Pathology:** - autosomal recessive - deficiency of GPIb receptor for vWF ==> impaired platelet adhesion to vWF **Symptoms:** - epistaxis, mucosal bleeding, easy bruising **Labs:** - thrombocytopenia - giant platelets on smear - prolonged bleeding time - normal PT and PTT - decreased platelet aggregation to ristocetin (induces binding of vWF and GPIb) - ADP aggregation, epinephrine aggregation, collagen aggregation **Treatment:** - supportive - platelet transfusion

Answer 14

**Pathology:** - autosomal recessive - deficiency/abnormality of platelet GIIb/IIIa (fibrinogen receptor) ==> platelets unable to aggregate **Symptoms:** - mucocutaneous microhemorrhages, epistaxis, petechiae/purpura **Labs:** - normal platelet morphology on smear - absent platelet aggregation to ADP, collagen, epinephrine - normal aggregation to ristocetin **Treatment:** - platelet transfusions

Answer 15

**Pathology:** - autosomal recessive - deficient platelet granule contents: alpha, delta, or both - decreased platelet secretion - decreased secondary wave of platelet aggregation **Symptoms:** - mild, lifelong bleeding symptoms **Labs:** - gray appearing platelets in smear due to absence of alpha granules - prolonged bleeding time - normal PT and PTT - normal ristocetin - no second wave in ADP and epinephrine aggregation; impaired collagen aggregation **Treatment:** - anticipating and preventing risks of bleeding

Answer 16

**Pathology:** - autoantibodies (usually IgG) directed against GpIIb/IIIa or GpIb bind to platelet surface - platelets being destroyed **Symptoms:** - easy bleeding, petechiae, epistaxis - acute ITP: self limited, seen in children after viral infections - chronic ITP: tends to affect women between 20-40 **Labs:** - large platelets on smear <- megakaryotes stimulated due to platelets being destroyed - increased bleeding time - normal PT and PTT - coagulation factors unaffected **Treatment:** - Prednisone (immune suppressant) - splenectomy

Answer 17

**Pathology:** - ADAMTS13 (protease) deficiency ==> abnormally large vWF multimers that activate platelets - vWF multimers remain attached to endothelial cells ==> platelet adhesion, aggregation, microvascular thrombosis - usually due to acquired antibodies **Symptoms:** - occurs primarily in adults - skin and mucosal bleeding - classic pentad: thrombocytopenia, microangiopathic hemolytic anemia, neurologic impairment, fever, renal dysfunction **Labs:** - erythroid progenitors (nucleated RBCs) and schistocytes, thrombocytopenia - increased bleeding time - normal PT and PTT - coagulation factors unaffected **Treatment:** - plasma exchange using FFP - corticosteroids

Answer 18

**ITP**: disorder of platelet destruction governed by platelet autoantibodies **TTP**: disorder of platelet consumption and microthrombi formation resulting in organ ischemia

Answer 19

- irreversibly inhibits platelet cyclooxygenase (normally induces platelet activation) - normal platelet count - Low dose aspirin is good: it irreversibly inhibits platelet and endothelial cell TXA2 synthesis - Endothelial cells can synthesize new enzyme and produce PGI, but platelets cannot recover

Answer 20

- von Willbrand deficiency - Disseminated intravascular coagulation (DIC) - Hemophilia A & B - Vitamin K deficiency

Answer 21

**Pathology:** - Types 1-3 vWF deficiency: 1 = slight decrease, 2 = qualitative, 3 = absent - vWF binds to exposed collagen at site of injury => GpIb receptors on platelets bind to vWF => activation of GpIIb/IIIa => platelets crosslink - vWF is carrier protein for FVIII **Symptoms:** - primary hemostasis impairment - secondary hemostasis impairment (prolonged PTT that may not see mixing correction) - mucosal bleeding, superficial bleeding **Treatment:** - Desmopressin (vasopressin)

Answer 22

**Pathology:** - Systemic activation of clotting cascade ⇒ increased consumption of clotting factors and platelets ⇒ exhaustion of clotting factors - syndrome secondary to sepsis, obstetric disasters, malignancies, leukemia, snake bites, heat stroke, brain injury, transfusion reaction, etc. **Symptoms:** - clotting and bleeding can dominate - prolonged PT and PTT - D-dimer positive (fibrin degradation product) - low factors V & VIII, low platelets, low fibrinogen (clot) **Treatment:** - treat underlying cause

Answer 23

**Pathology:** - X-linked deficiencies - Hemophilia A = factor VIII deficiency - Hemophilia B = factor IX deficiency - inhibitors can develop after previous exposure (mixing study would be positive) **Symptoms:** - prolonged PTT, mixed study negative (corrects) - hemarthrosis (hemophilia of joint spaces, deep tissue) **Treatment:** - replacement of deficient factor - prophylaxis, on demand therapy

Answer 24

**Pathology:** - malnutrition, alcohol use disorder - vitamin K-dependent factors are deficient: factors II, VII, IX, X **Symptoms:** - PT affected more than PTT

Answer 25

- Factor V Leiden mutation - prothrombin mutation - protein C & S deficiency - antithrombin III deficiency

Answer 26

- autosomal dominant - point mutation abolishes binding site for protein C => factor V resistant to degradation => increased risk for venous thrombosis - common (> 1%)

Answer 27

- autosomal dominant - G20210A mutation causes increased prothrombin (factor II) expression => hypercoagulation - common

Answer 28

- normally, protein C complexes with protein S to inhibit factors V and VIII => degradation of thrombus - both vitamin K-dependent <- would expect protein C/S levels to be low in a patient on warfarin - if pt with low protein C is started on warfarin, increased risk of clotting => superficial necrosis of skin (breasts) - rare

Answer 29

- too little or abnormal antithrombin III produced => decreased inhibition of coagulation - rare

Answer 30

Used prior to blood transfusions **Type and screen**: performed when blood may be needed - front type: using reagent anti-A/anti-B Abs to type for antigens on RBC - back type: using reagent A and B RBC type for matching Ab in plasma **Type and crossmatch**: performed with blood is definitely needed - blood units are reserved and tested for ABO and Rh compatibility

Answer 31

**Pathology:** - Rh(D) negative mom is exposed to Rh(D) positive fetal cells, stimulating mom to make anti-Rh(D) IgG antibodies - first pregnancy is stimulus for immunization; often not affected **Symptoms:** - fetal RBCs attacked by mom's anti-Rh(D) antibodies ==> fetal anemia - baby can be born with jaundice (high bilirubin) and anemia **Treatment:** - Rh(D) negative mom should receive pooled IgG anti-Rh(D) at 28wks and within 72hr postpartum - if fetal anemia develops: transfusion of washed group O RBC intrauterine to baby - if fetus born with anemia and jaundice: neonatal exchange transfusion (removal of whole blood and replacement with group O Rh- RBC and AB plasma)

Answer 32

**Direct antiglobulin test:** - detects antibodies already bound to blood RBCs - pt's blood sample is directly used and washed, then incubated with Coomb's reagent (C3, antihuman Ab) ==> RBCs agglutinate - positive DAT = pt's RBCs have auto IgG antibodies and/or C3 on them - ex: to detect hemolytic anemia **Indirect antiglobulin test:** - detects serum antibodies that might bind to RBCs - recipient serum is combined with donor blood sample ==> recipient Igs form complexes with donor RBCs ==> C3 added to agglutinate targeted RBCs - cross-match testing, maternal serum testing

Answer 33

To ensure bone marrow donor is a match with recipient: - mix blood mononuclear cells from 2 persons (donor and recipient) in tissue culture - bone marrow recipient APC presents MHC I/II, which is recognized by donor T lymphocytes - MHC I would stimulate CD8+ CTL proliferation - MHC II would stimulate CD4+ helper T cell proliferation - measure lymphocyte proliferation in vitro ==> less proliferation of T cells is good

Answer 34

- acute hemolytic transfusion reaction (AHTR) - delayed hemolytic transfusion reaction (DHTR) - febrile non-hemolytic transfusion reaction (FNHTR) - allergic and anaphylactic transfusion reaction - septic transfusion reaction - transfusion-associated circulatory overload (TACO) - transfusion-related acute lung injury (TRALI) - post-transfusion purpura (PTP) - transfusion-associated graft vs. host disease (TA-GVHD)

Answer 35

**Pathology:** - preformed RBC antibody (pt has hx of transfusions) reacts with donor RBC - complement activation => membrane lysis => release of free Hb, IgM **Symptoms:** - intravascular hemolysis < 24hr after transfusion - fever, hypotension, shock, pink/red urine - 40% mortality - negative DAT (direct antibody test) due to all incompatible cells hemolyzed; positive urine hemoglobinuria, schistocytes **Treatment:** - stop transfusion, support BP - protect kidneys: IV fluids, diuretics

Answer 36

**Pathology:** - new alloantigen develops in pt post-transfusion - no complement activation; instead, cells destroyed via phagocytosis (reticuloendothelial system) ==> extravascular hemolysis **Symptoms:** - progressive anemia 3 days-3wk after transfusion - may present with fever, jaundice, dark urine - positive DAT, positive new antibody **Treatment:** - transfusion of antigen-free RBCs

Answer 37

**Pathology:** - cytokines released from donor lymphocytes accumulate in bag during storage ==> antibodies in recipient plasma react **Symptoms:** - temperature increase of >1C (fever may be only symptom) - often accompaniesd by chills / rigors **Treatment:** - increased risk due to previous alloimmunization to HLA - prevention: leukoreduction (remove WBCs), premedicate with acetaminophen

Answer 38

**Allergic:** - pts develop urticaria (hives), flushing, pruritus (itching) - due to recipient IgE reacting to donor plasma proteins - Tx: stop transfusion, give antihistamine, may restart once symptoms resolve **Anaphylactic:** - pts develop urticaria, wheezing low BP - due to recipient IgA reacting to donor plasma proteins - Tx: stop transfusion, start epinephrine, antihistamines, corticosteroids - Prevention: wash donated RBCs/platelets

Answer 39

**Pathology:** - bacteria in donor blood - higher risk in platelet transfusions (platelets stored in room temp) **Symptoms:** - fevers, rigors, drop in BP, increase in HR **Treatment:** - broad spectrum abx until organism identified

Answer 40

**Pathology:** - transfusion ==> expansion of intravascular volume ==> pulmonary edema - increased risk in those with heart failure, renal insufficiency **Symptoms:** - acute hypertension (increase in blood volume) - jugular venous distension (backup of blood from heart into veins) - elevated brain natriuretic peptide - usually NO fever - CXR: pulmonary edema **Treatment:** Prevention: decrease rate of transfusion (slowly over 4hr)

Answer 41

**Pathology:** - donor anti-HLA antibodies and/or anti-neutrophil antibodies passed onto recipient ==> recipient granulocytes release proinflammatory mediators ==> increased vascular permeability ==> pulmonary endothelium damage, fluid extravasion into lungs - usually FFP or platelets **Symptoms:** - within 6hr of transfusion: fever, tachycardia, hypotension, hypoxemia (low blood O2) - CXR: new bilateral infiltrate **Treatment:** - supportive - prevention: no FFP from any female donors

Answer 42

**Pathology:** - previously sensitized recipients (hx of transfusion, pregnancy) produce platelet-specific alloantibodies which may be autoreactive ==> thrombocytopenia - within 2wks of transfusion **Symptoms:** - purpura (bruising) - thrombocytopenia (10,000 platlets/uL) - mucosal bleeding (GI bleeding) common

Answer 43

**Pathology:** - different HLA antigens between donor (graft) and recipient (host) - functionally active immune cells must be present in donor blood product - host incapable of rejecting donor immune cells - high risk for immunocompromised recipients **Symptoms:** - onset 3-30 days after transfusion - rash (trunk => extremities), fever, watery diarrhea, elevated LFT (liver enzymes), pancytopenia - bone marrow failure - > 90% mortality within 1-3wk of symptom onset **Treatment:** - prevention: irradiation of products (inactivates donor lymphocytes)