Fa: Step 2 Ck. Hematology/oncology.

Front 1

activity of heparin

antidote?

Back 1

increase PTT
decrease fibrinogen
activates antithrombin III
affects intrinsic pathway

protamine sulfate

Front 2

activity of warfarin

antidote?

Back 2

increase PT
inhibits vitamin K
affects extrinsic pathway
teratogenic (crosses placenta)!

vitamin K

Front 3

activity of enoxaparin

Back 3

a LMWH, inhibits factor Xa
does not have to be monitored
QD/BID dosing

Front 4

why should patients being initiated on anticoagulation be started on heparin before warfarin?

Back 4

warfarin inhibits proteins C and S before vitamin K-dependent factors (II, VII, IX, and X) and therefore causes a transient period of paradoxical hypercoagulability before achieving its anticoagulant effects

Front 5

what is goal INR of anticoagulation?

Back 5

2.0-3.0

(2.5-3.5 if mechanical heart valve)

Front 6

describe the intrinsic and extrinsic pathways of the coagulation cascade

Back 6

Front 7

define hemophilia

etiology of this condition?

Back 7

deficiency of clotting factor that leads to bleeding diathesis

usually hereditary, but may be acquired through development of antibody to a clotting factor.

Front 8

presentation of hemophilia

Back 8

spontaneous hemorrhage into tissues and joints most commonly

spontaneous intracerebral hemorrhage, renal and retroperitoneal bleeding and GI bleeding may also be seen

mild cases may not present until after surgery or trauma

Front 9

lab values to Dx hemophilia

other tests?

Back 9

PT: usually normal
aPTT: prolonged (degree of prolongation is gauge of severity)
Thrombin, fibrinogen, bleeding time: usually normal

mixing study, specific assays for clotting factors (VII, VIII, IX, XI, XII)

Front 10

what levels of clotting factors correspond to hemophilia severity?

Back 10

mild: >5%
moderate: 1-3%
severe: <1%

Front 11

treatment for bleeding episodes in hemophilia?

Back 11

immediate transfusion of clotting factors (or cryoprecipitate) to 40% normal
BID Factor VIII (t1/2=12h), QD Factor IX (t1/2=24h)

desmopressin in mild cases (fluid restrict to avoid hyponatremia)

RBCs may be encessary

Front 12

what is the action of desmopressin (DDAVP) in the treatment of hemophilia?

Back 12

assists in release of extra factor VIII from body

Front 13

von Willebrand Disease (vWD):

etiology
clotting factors affected

Back 13

inherited in AD fashion

vWF normally carries factor VIII, but levels are low in vWD and patients are factor VIII deficient

the most common inherited bleeding disorder (1% of population affected)

Front 14

presentation of von Willebrand's Disease

Back 14

easy bruising
mucosal bleeding (e.g. epistaxis, oral bleeding)
menorrhagia
postincisional bleeding

NO PETECHIAE, Sx worsen with ASA use

Front 15

coagulation lab results in vWD?

Back 15

PT: normal
aPTT: prolonged

ristocetin cofactor assay of patient plasma can measure vWF's capacity to agglutinate platelets

Front 16

treatment of vWD bleeding episodes?

Back 16

DDAVP

menorrhagia can be controlled with OCPs

avoid ASAs and other inhibitors of platelet function

Front 17

most common inherited hypercoagulable state?

Back 17

factor V Leiden

a polymorphism in factor V, rendering it resistant to inactivity by activated protein C

Front 18

what are physiologic causes of hypercoagulable states?

Back 18

pregnancy
advanced age

Front 19

what complications are associated with hypercoagulable states?

Back 19

complications are RECURRENT:
DVT, PE, arterial thrombosis, MI, stroke

women may have recurrent spontaneous abortions

Front 20

what is the workup for a hypercoagulable patients?

Back 20

lupus antigen/antiphospholipid syndrome
antithrombin III deficiency
protein C and S deficiencies
activated protein C resistance
homocysteine elevation
prothrombin G20210A mutation

Front 21

what are the two most common forms of acquired coagulopathy?

Back 21

1. liver disease (most common)
2. DIC

Front 22

what is the characteristic dual nature of DIC?

what is the pathophysiology?

Back 22

thrombosis AND hemorrhage

caused by deposition of fibrin in small blood vessels, leading to thrombosis and end-organ damage; depletion of clotting factors leads to a bleeding diathesis

may be associated with almost any severe illness

Front 23

acute v. chronic DIC: presentation

Back 23

acute: generalized bleeding out of venipuncture sites, into organs; ecchymoses and petechiae

chronic: bruising and mucosal bleeding, thrombophlebitis, transient neurologic syndromes

Front 24

acute v. chronic DIC: lab values

Back 24

acute: PT, aPTT, thrombin time, and D-dimer are ELEVATED
platelets and clotting factors are DECREASED

chronic: PT, aPTT, thrombin time, and D-dimer are ELEVATED
platelets and clotting factors are NORMAL

Front 25

thrombotic thrombocytopenis purpura (TTP): related diseases

Back 25

hemolytic-uremic syndrome (HUS)
hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome

Front 26

TTP: pathogenesis

Back 26

platelet microthrombi (uncertain origina) block of small blood vessels leading to end-organ ischemia and dysfunction; RBCs lysed by contact with microthrombi (microangiopathic hemolytic anemia)

Front 27

TTP: history

Back 27

clinical syndrome; 5 S/Sx

1. low platelets
2. microangiopathic hemolytic anemia
3. neurologic changes (delirium, seizure, stroke)
4. impaired renal function
5. fever

Front 28

TTP: diagnosis

Back 28

assess for the 5 clinical signs (it is rare that all are present)

assess for schistocytes/nucleated RBCs on peripheral blood smear

labs for hemolytic anemia (high indirect bili, LDH, AST; low haptoglobin)

coagulation labs are normal

Front 29

severe elevation of Cr: more common in TTP or HUS?

Back 29

HUS, which is characterized by renal FAILURE (v. impairment in TTP)

Front 30

how to distinguish DIC v. TTP?

Back 30

coagulation studies: PT and aPTT prolonged in DIC, normal in TTP

Front 31

TTP: treatment

Back 31

corticosteroids, plasma replacement, plasmapheresis

DO NOT GIVE PLATELETS

Front 32

idiopathic (immune-mediated) thrombocytopenic purpura: basic characteristics

Back 32

characterized by presence of anti-platelet IgG antibodies

causes decreased platelet count; bone marrow responds by increasing platelet production with increased megakaryocytes seen in the BM

THIS IS THE MOST COMMON IMMUNOLOGIC DISORDER IN WOMEN OF CHILDBEARING AGE

Front 33

ITP: typical patient history and associated diseases

Back 33

patients often feel well; no systemic Sx
minor mucocutaneous bleeding, easy bruising
associated with lymphoma, leukemia, SLE, HIV, HCV

Front 34

ITP: presentation

Back 34

may be acute or chronic

acute: abrupt onset of hemorrhage following viral illness (commonly affecting kids 2-6 years)

chronic: insidious onset not related to infection; affects primarily women ages 20-40

Front 35

ITP: diagnosis

Back 35

Dx of exclusion; rule out other causes of thrombocytopenia first

Front 36

ITP: treatment

Back 36

Tx is reserved for patients with spontaneous bleeding:

corticosteroids, high-dose IVIG; splenectomy if refractory to these

Front 37

anemia: definition

MCV values to classify anemia

Back 37

low Hct and Hb

microcytic: <80 fL
normocytic: 80-100 fL
macrocytic: >100 fL

Front 38

iron deficiency anemia:

give MCV. who is most commonly affected?

Back 38

<80 (microcytic)

toddlers, adolescent girls, women of childbearing age, anyone with chronic GI blood loss

Front 39

iron deficiency anemia: Sx

Back 39

fatigue
weakness
brittle nails
pica

patients may be asymptomatic if the anemia develops slowly

Front 40

iron deficiency anemia: physical exam findings

Back 40

glossitis
angular cheilitis
koilonychia (spoon nails)

Front 41

iron deficiency anemia: Dx

Back 41

BM biopsy is gold standard but rarely done
iron studies (iron, TIBC/transferrin, ferritin, serum transferrin receptor)
blood smear showing hypochromic, microcytic RBCs

Front 42

iron deficiency anemia versus anemia of chronic disease: labs

Back 42

iron deficiency anemia:
iron -- L
TIBC/transferrin -- H
ferritin -- L
serum transferrin receptor -- H

anemia of chronic disease:
iron -- L
TIBC/transferrin -- L
ferritin -- H
serum transferrin receptor -- normal

if both conditions present, looks more like iron deficiency:
iron -- L
TIBC/transferrin -- normal or H
ferritin -- normal or L
serum transferrin receptor -- normal or H

Front 43

iron deficiency anemia: Tx

Back 43

replacement iron for 4-6 months

oral iron may cause GI problems; antacids may interfere with iron absorption

Front 44

why do B12 and folate deficiency lead to megaloblastic anemia?

Back 44

deficiency interferes with DNA synthesis, leading to a delay in blood cell maturation and increase in blood cell size

Front 45

what conditions lead to deficiency of B12 and folate?

Back 45

B12: usually pernicious anemia (destruction of parietal cells and thus lack of intrinsic factor

folate: dietary insufficiency, malabsorption, alcoholism, certain drugs

drugs that interfere with DNA synthesis (e.g. some chemotherapeutics) may lead to megaloblastic anemia

Front 46

presentation of B12 (cobalamin) or folate deficiency

Back 46

fatigue
pallor
diarrhea
loss of appetite
headaches
tingling/numbness of hands and feet

B12 (cobalamin) deficiency may lead to a demyelinating disorder with motor, sensory, autonomic and/or neuropsychiatric dysfunction (subacute combined degeneration of the cord)

Front 47

B12 or folate deficiency: Dx

Back 47

peripheral smear shows elevated MCV; hypersegmented granulocytes might be present

Front 48

B12 versus folate deficiencies: levels of methylmalonic acid (MMA) and homocysteine

Back 48

B12 deficiency: elevated MMA, elevated homocysteine

folate deficiency: normal MMA, elevated homocysteine

Front 49

hemolytic anemia: typical MCV

Back 49

80-100 fL (it is a normocytic anemia!)

Front 50

hemolytic anemia: etiologies

Back 50

G6PD deficiency (X-linked recessive transmission)
paroxysmal nocturnal hemoglobinuria
hereditary spherocytosis
autoimmune RBC destruction (after EBV or mycoplasma infection, CLL, rheumatoid arthritis, medications)
sickle cell disease
microangiopathic hemolytic anemia (TTP, HUS, DIC)
mechanical hemolysis
malaria, hypersplenism

Front 51

hemolytic anemia: presentation

Back 51

pallor
fatigue
tachycardia
tachypnea
patients typically jaundiced, with low haptoglobin and elevated indirect bilirubin, LDH
dark urine of hemoglobinuria
elevated reticulocyte count

Front 52

hemolytic anemia: Tx

Back 52

corticosteroids, iron supplementation

steroids address immunologic causes, iron replaces urinary losses; splenectomy or transfusion in refractory/severe cases

Front 53

problem in aplastic anemia and underlying cause

Back 53

destruction of bone marrow cells means failure of blood cell production

Front 54

etiology of aplastic anemia

Back 54

multiple:

hereditary (Fanconi)
autoimmune
viral (HIV, Parvovirus B19)
toxins
radiation

Front 55

history/exam in aplastic anemia

Back 55

pallor
weakness
tendency to infection (most dangerous feature!)
petechiae
bruising
bleeding

Front 56

Dx of aplastic anemia

Back 56

clinical presentation and CBC
verification with BM biopsy

Front 57

physical exam in Fanconi anemia

Back 57

café au lait spots
short stature
radial/thumb hypoplasia/aplasia

Front 58

aplastic anemia: Tx

Back 58

blood transfusion
stem cell transplant
cyclosporin A + anti-thymocyte globulin (immunosuppress)

Front 59

sickle cell disease (SCD): transmission and underlying defect

Back 59

AR inheritance; mutation in adult hemoglobin (glu-val missense in Beta chain of globin)

Front 60

characteristics of RBCs in SCD

Back 60

decreased RBC survival
tendency of sickled cells to vaso-occlusion

Front 61

early complications of SCD

Back 61

asymptomatic in first two years of life

later hemolysis results in anemia, jaundice, cholelithiasis, high cardiac output (--> murmur and cardiomegaly), and delayed growth

Front 62

why does spleen auto-infarct in SCD?

Back 62

chronic vaso-occlusion by sickled cells leads to ischemic organ damage and infarction

Front 63

common triggers of vaso-occlusive crises in SCD

Back 63

cold temperatures
dehydration
infection

Front 64

what is common trigger of aplastic crisis in SCD?

Back 64

parvovirus B19 infection

Front 65

Dx of SCD

Back 65

blood smear shows sickle cells and target cells
gold standard is quantitative Hb electrophoresis

Front 66

mechanism of hydroxyurea in SCD

Back 66

stimulates Hb F production

hydroxyurea is teratogenic!

Front 67

Tx for SCD and complications

Back 67

hydroxyurea
chronic transfusion therapy
cholecystectomy for cholelithiasis

VOCs:
pain management, O2, IV fluid rehydration, abx

Front 68

Dx of thalassemias

Back 68

Hb electrophoresis

Front 69

Why are chelators (e.g. deferoxamine) given to transfusion dependent beta-thalassemia major patients?

Back 69

to prevent iron overload

Front 70

"hyperviscosity syndrome" features

Back 70

easy bleeding/bruising
blurred vision
neurologic abnormalities
plethora
pruritus
hepatosplenomegaly
CHF

Front 71

causes of primary erythrocytosis?

Back 71

hypoxia (lung disease, smoking, altitude)

polycythemia vera (clonal proliferation of pluripotent stem cell)

Front 72

Treatment for polycythemia vera?

Back 72

phlebotomy for symptoms

ASA (for thromboprophylaxis)

cytoreductive drugs such as hydroxyurea or IFN

Front 73

Tx for transfusion reactions

Back 73

First, stop the transfusion. Then:

nonhemolytic febrile: Tylenol

minor allergic: antihistamines (then epi, then steroids)

hemolytic: volume replacement, diuretics and pressors