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Flashcards in Hematology Deck (111):

What triggers RBCs to sickle in affected individuals?

Low O2 states


Why are sickle cells bad - how do they cause harm?

Vasoocclusion of organs/tissues


How does acute chest syndrome present?

Pulmonary infiltrates on CXRFever, hypoxia, acidosisNo infection


What is the typical electrophoresis in sickle cell disease and trait?

SS: Mostly Hgb S, some A2 and FTrait: Mostly Hgb A noted, with some S, A2, and F


Who should be offered sickle cell carrier screening?

Those of African and mediterranean ancestry


How should you screen for sickle cell in those with African or other heritage?

African-American: CBC + electrophoresisOther: CBC with diff, and electrophoresis only if microcytic (<80)


What are the risks associated with sickle cell disease in pregnancy?

PTL, PPROM, infection post-partum, IUGR, IUFD


How much folic acid should patients with sickle cell take daily?



How do you counsel patients with sickle cell on crisis avoidance?

Avoid triggers (cold, physical exertion, dehydration, and stress)


Can hydroxyurea be used in pregnancy to avoid a sickle crisis?

No - hydroxyurea is teratogenic


How do we treat sickle crises?

O2, opiodsEvaluation/treatment of cause (infection, dehydration)Management of compliations (acute chest)


When exchange transfusions are utilized in pregnancy for sickle cell, what is the typical indication?

Reduce frequency of pain crises


With an exchange transfusion, what is the treatment goal for % HgbS?

Hgb S <40%


How should we monitor fetuses in pregnancies complicated by SS?

Serial growth ultrasound q 4-6 weeksAntepartum testing beginning at 32 weeks


What electrophoresis pattern is consistent with beta-thalassemia?

Increased Hgb A2 > 3.5%, increased Hgb F, no Hgb S


What causes B-thal?

Bad beta-chain -> loss of type A Hgb (alpha/beta)


What are the two general types of gene mutations associated with B-thal?

B (0) - absent beta chain productionB (+) - decreased amount of beta chain production


What are the two grades of B-thal severity?

B-thal MINOR: mild anemiaB-thal MAJOR: severe anemia, complications


What complications are associated with B-thal major over a lifetime (outside of pregnancy)

Extramedullary hematopoeisisDelayed sexual development (due to hemosiderin deposition in hypothalamus)Poor growthDeath by age 10 if blood transfusions are not initiated


What patients with B-thal major are candidates for pregnancy?

Normal heart functionNo end organ damage from chronic transfusion (or h/o transfusion, coupled with deferoxamine for chelation)


Which ethnicities are most commonly associated with B-thal mutations?

Mediterranean, Asian, middle eastern, Hispanic, W.Indian


What is the outcome of B-thal combined with HgbS?

Severe anemia due to absent functional beta-chain production -> no Hgb A production


While pregnancies with B-thal minor are usually favorable, what outcomes should be monitored for?

IUGR, oligohydramnios


Instead of iron, what supplement should be given to women with B-thal?

Folic acid 1mg/day


If you diagnose a patient with B-thal, what supplement should be initiated, and who else should be tested?

Initiated folic acid 1mg/dayTest father with CBC -> electrophoresis if microcyticGenetic counseling if dad also a carrier


When should you refer a patient for alpha-thal testing?

Microcytic anemiaNormal electrophoresis and iron testingSE Asian, African, W Indian, and mediterranean


What causese alpha-thalassemia?

Defunct alpha-chain production -> decreased Hgb A (alpha/beta), A2 (alpha/delta), and F (alpha/gamma)


Alpha thall involves mutations in how many alpha genes? What are the possible mutation combinations called?

TRANS: a_/a_CIS: __/aa


What ethnicities are most likely to be affected by sickle cell?

SE Asian, African, W. Indian, Mediterranean


Why are E.Asian individuals with a-thall more likely to have a child with Hgb Barts than African individuals?

CIS mutation (__/aa) seen more commonly in SE Asia -> more likely to have fetus with (__/__)


What is the outcome of Hgb Barts?

Fetal hydrops, IUFD, preeclampsia


Does a-thal worsen or improve sickle cell?

A-thal improves presentation of sickle cell, as less Hgb S (alpha/sickle) can be produced!)


Normal plasma iron level

40-175 mcg/dL


Normal plasma TIBC

216-400 mcg/dL


Normal transferrin saturation



Normal serum ferritin level

> 10 mcg/dL


Definition of anemia in 1st or 3rd trimester

Hgb < 11 g/dL


Definition of anemia in 2nd trimester

Hgb < 10.5 g/dL


Physiologic changes in RBC mass and plasma in pregnancy

RBC mass and plasma both increase, but the plasma increase (50%) is proportionally greater than the RBC increase (15-30%)


Initial workup of anemia

CBC with Hgb and mean corpuscular volume


Workup if Hgb < 11 g/dL and MCV < 80 um3

Microcytic anemiaObtain Hgb electophoresis and serum ferritin


Workup if Hgb < 11 g/dL and MCV > 80 um3

Retic count, history - active bleeding, med exposure, chronic dz, G6PD deficiency, fam hx of RBC disorders


Workup if high reticulocyte counts

Anemia may be due to hemolysis or blood lossConsider:Peripheral blood smearHaptoglobinDirect coombs for autoimmune hemolytic anemiaElectrophoresisHemoccult


Most common cause of anemia in pregnancy

Iron deficiency


Diagnosis of iron deficiency anemia

MCV < 80Decreased serum ironIncreased TIBC (>400 mcg/dL)Decreased serum ferritin (<30 mcg/L)


Complications of iron deficiency in anemia in pregnancy

Low birth weightPreterm birthMaternal CV compromiseNeed for transfusionPostpartum depressionPoor mental and psychomotor performance testing in offspring


Dosing of IV iron sucrose

Weight before pregnancy (kg) x (110g/L - actual hemoglobin g/L) x 0.24 + 500 mg


Is anemia of chronic disease normocytic or microcytic?

Usually normocytic (20% microcytic)


Diagnosis of anemia of chronic disease

Decreased serum ironNormal or increased serum ferritinDecreased TIBC


Causes of anemia of chronic disease

Chronic liver diseaseThyroid diseaseUremiaChronic infectionsMalignancies


Workup of anemia of chronic disease

LFTsBUN/CrTSHTests for malignancy or chronic infxn as indicated by hx/physIron, B12, folate to rule out combine deficiencies


Iron studies in thalassemia

Normal or increased serum ironNormal or increased TIBC


Common ancestries for alpha-thalassemia

Southeast Asian


Diagnosis of alpha-thalassemia

Probable alpha thal:MCV < 80Nl Fe studiesHgb A2 on electrophoresis < 3.5% Confirm with DNA probe, consider testing of father/prenatal dx


Common ancestries for beta-thalassemia

MediterraneanAsianMiddle EasternHispanicWest Indian


Diagnosis of beta-thalassemia

MCV < 80Nl Fe studiesHgb A2 on electrophoresis >3.5%Consider testing of father, prenatal dx if +, Hb electrophoresis at one year of age if negative


Recommended dietary allowance of ferrous iron during pregnancy

27 mg, present in most prenatal vitamins


Definition of macrocytic anemia

MCV > 100 fL


Causes of macrocytic anemia

Levels greater than 115 fL are almost exclusively seen in patients with folic acid or vitamin B12 deficiencies


Diagnosis of B12 deficiency

<100 pg/mL


Diagnosis of folate deficiency

RBC folate < 150 ng/mL


Causes of folate deficiency

Diets deficient in fresh leafy vegetables, legumes, or animal proteins.


Folic acid requirements in pregnancy

Increase from 50 mcg to 400 mcg per day


Treatment of pregnancy-induced folic acid deficiency

Nutritious diet, folic acid and iron supplementation1 mg folic acid/day


Causes of vitamin B12 (cyanocobalamin) deficiency

Partial or total gastric resection, Crohn's disease


Treatment of B12 deficiency

Monthly IM injections of 1000 mcg B12


What is the most common inherited bleeding disorder?

von Willebrand disease (vWD)Usually autosomal dominantAffects 1% of screened population


What is von Willebrand factor?

Binds to platelets and endothelial components, forming an adhesive bridge at sites of endothelial injury.Contributes to fibrin clot formation by acting as a carrier protein for factor VIII, which has a greatly shortened 1/2 life and abnormally low concentration unless it is bound to vWF.


What is ristocetin?

Ristocetin is an antibiotic previously used to treat staphylococcal infections. It is no longer used clinically because it caused thrombocytopenia and platelet agglutination. It is now used solely to assay those functions in vitro in the diagnosis of conditions such as vWD and Bernard-Soulier syndrome. Platelet agglutination caused by ristocetin can occur only in the presence of von Willebrand factor multimers, so if ristocetin is added to blood lacking the factor or its platelet receptor, the platelets will not clump.


What are the 3 initial tests for vWD?

Plasma vWF antigen (vWF:Ag)Plasma vWF activity (ristocetin cofactor activity, vWF:Rco - bind to platelets in presence of ristocetin, or vWF:CB - binding to collagen)Factor VIII activity


If one of the 3 initial tests for vWD is abnormal, what should be done next?

vWF multimer distribution using gel electrophoresisRistocetin-induced platelet aggregation (RIPA - tests ability of pt's vWF to bind to platelets in suboptimal ristocetin concentrations)


What is Type 1 vWD?

Most common variant (75%), AD inheritancePartial quantitative deficiency of vWFClinical presentation varies from mild to severeLabs: concordant decr in vWF antigen, vWF activity (ristocetin cofactor), factor VIII activity, all vWF multimers are present but decreased


What is Type 2A vWD?

10-15% of cases, AD, mod-severe bleedingDecreased high & intermediate molecular weight multimers of vWFLabs: Ristocetin cofactor activity lower than the vWF antigen (ratio <0.5 ot 0.7); antigen may be in nl range; factor VIII levels nl or reduced; RIPA is reduced.


What is Type 2B vWD?

5% of cases, AD, mod-severe bleedingvWF has a gain of fxn mutation -> the larger multimers bind more readily to the platelet receptor, taking them out of circulation. May also have thrombocytopenia.Labs: discordant vWF:Ag & ristocetin cofactor activity, nl or decr Factor VIII


What are Type 2M & 2N vWD?

Uncommon variants with severe bleeding


What is Type 3 vWD?

Rare, severe bleeding involving skin, mucosal membranes, soft tissues, jointsLabs: marked decr or absence of detectable vWF, Factor VIII activity 1-10% of nl, ristocetin cofactor not detectable, RIPA is absent.


What is the difference between low vWF vs Type 1 vWD?

A diagnosis of Type 1 vWD requires vWF activity & antigen < 30 IU/dL. Individuals with mild bleeding symptoms and mildly decr vWF levels are referred to as having "low vWF."


What is the presentation of vWD?

Easy bruising, skin bleeding, prolonged bleeding from mucosal surfaces, menorrhagia. Exceptions: -Type 2N vWD - mimics classic hemophilia (soft tissue, joint, urinary bleeding, bleeding after invasive procedures)-Type 3 vWD - both mucocutaneous and joint/soft tissue bleeding


What can precipitate bleeding in patients with mild vWD?

Ingestion of aspirin or NSAIDS


What disorders are associated with acquired vWD?

SLE - antibodies to vWFHypothyroidism - decreased synthesisAortic stenosis - intravascular shear forcesLeukemiaUremiaHemoglobinopathiesValproic acid, ciprofloxacin


When should acquired vWD be suspected?

Onset of bleeding later in life-Hx of prior uneventful surgery prior to bleeding episode-Presence of an inhibitor to vWF or vWF-binding antibodies-Remission of bleeding after tx of an underlying acquired VWD-associated disorder-Response to treatment with IVIG-Short-lived Response to vWF-containing concentrates or desmopressin


How is inherited vWD treated?

5 classes of meds:Desmopressin (dDAVP) - promotes release of vWFReplacement therapy with vWF-containing concentratesAntifibrinolytic drugsTopical therapy w/ thrombin or fibrin sealanEstrogen therapyThere is a role for recombinant human factor VIIa in pts with severe Type 3 vWD who develop inhibitors to replacement vWF.


How is acquired vWD treated?

Depends on pathogenesis, may consider trial of dDAVP, vWF replacement, IVIG, recombinant VIIa


How does pregnancy affect vWD?

-Levels of VWF rise in normal individuals and in most patients with VWD during the second and third trimesters to two to three times baseline. Consequently, many patients with VWD reach normal levels of both VWF and factor VIII at term. However, the qualitative abnormalities in type 2 VWD will persist and thrombocytopenia in type 2B VWD may worsen. -Procedures such as amniocentesis, chorionic villus sampling, and regional anesthesia are generally safe if these levels are maintained and the coagulation screen is otherwise normal. -Since desmopressin has a theoretical possibility of initiating uterine contractions, it is not generally used prior to delivery. However, limited data indicate that dDAVP has been used "without mishap" in 31 pregnant women for prophylaxis before invasive procedures.


What are delivery considerations for women with vWD?

-Although treatment is not needed during pregnancy in the majority of women with VWD, many require treatment during delivery and during the following one to three weeks thereafter. -It is recommended that levels of VWF and factor VIII be maintained at 50 IU/dL or higher during delivery and for at least three to five days after delivery. -An anesthesia consultation should be obtained prior to the onset of labor to discuss options for regional anesthesia or analgesia. ----Regional anesthesia may be considered when VWF and factor VIII levels are maintained at about 50 IU/dL.-Low factor VIII appears to be the most important determinant of increased bleeding during delivery. It is generally recommended that factor VIII levels be at or above 50 percent for a cesarean section. -Cesarean delivery should be reserved for the usual obstetrical indications; fetal intraventricular hemorrhage due to maternal or fetal VWD is rare. -Elective surgical procedures on the newborn (eg, circumcision) should be delayed until the infant's VWD and factor VIII status have been determined.


How should women with VWD be managed postpartum?

-Plasma levels of factor VIII and VWF fall quickly after delivery and excessive bleeding may occur at this time. -The average time of onset for postpartum hemorrhage in women with VWD is from 11 to 23 days post delivery. -Thus, dDAVP or VWF replacement may be required during or shortly after delivery, and for the first 2-4 weeks thereafter.


What is the most common congenital bleeding disorder in humans?

vWF (1% of the population)


Type I vWD

AD, quantitative defect, menorrhagia common.


Type 2 vWD

AR, qualitative defect, heavy menorrhagia


Type 3 vWD

AR, quantitative defect, heavy menorrhagia


Only finding in Type 2B vWD

Isolated thrombocytopenia


What is von Willebrand factor?

A multimeric glycoprotein that serves as a carrier protein for factor VIII.


How is vWD diagnosed?

Factor VIII level 15-30% of normal, prolonged bleeding time, decreased APTT (occasionally, lack of ristocetin-induced platelet aggregation, abnl platelet adhesiveness, Factor VIII coagulant activity to factor VIII antigen ratio of 1, and thrombocytopenia (in 2B).


How is the risk of bleeding in vWD predicted?

The concentration of VIII:C predicts postpartum hemorrhage: if greater than 50% of normal, and normal bleeding time, then the risk is minimal.


What is the treatment of choice in vWD Type 1?

Intranasal DDAVP is now the treatment of choice in Type I and cryo if patients fail to respond. In patients with PPH, IV DDAVP should be given.


What is the treatment of choice in vWD Types 2 & 3?

Cryoprecipitate - contains Factor VIII, Protein C, and Ristocetin cofactor


When should treatment for vWD be initiated?

Factor VIII levels below 25% of normal.


What is the most common cause of severe thrombocytopenia in the newborn?

Sensitization to HPA-1a (PLA-1) antigen - the etiology in 3/4 of cases of NAIT.


Recurrence rate for NAIT?



Normal alpha-globin genotype



alpha+ thalassemia heterozygotes - genotype & phenotype

-a/aa or aa/-a: silent carrier
'-a/-a: alpha-thal minor - mild hypochromic microcytic anemia (more common in African Americans)


alpha0 thalassemia heterozygote - genotype & phenotype

--/aa: mild hypochromic microcytic anemia (more common in Asian Americans)


Compound heterozygous alpha0/alpha+ - genotype & phenotype

--/a: Hgb H (B4), moderate to severe hemolytic anemia


Homozygous alpha-thalassemia

--/--: Hgb Bart (Y4), hydrops fetalis


Which decreases the likelihood of alpha-thalassemia?

a) Southeast Asian (Southeast Asian, African, and West Indian descent)
b) African American
c) HgbA2 <2.0% (A2 is elevated in BETA-thal)
d) 125 mcg/dL (not specified what this is measuring!)


Sickle cell involves a mutation of which Hbg type and side chain?

Hgb A, beta chain (glutamic acid -> valine)


How common is sickle cell trait?

1/12 African Americans


Aside from African Americans, who is at risk for carrying the sickle cell mutation? (ethnicity-wise)

Those from Greece, Italy, the Middle East, and East India


What coagulation factors are increased in pregnancy?

(1, 7, 8, 9, 10)


What coagulation factors are decreased in pregnancy?



What coagulation factors are unchanged in pregnancy?

(2, 5, 12)