12) Hemolytic anemia—nonimmune defects

Question 1

2 types of extrinsic factors that can cause hemolytic anemia

Answer 1

• immune
• nonimmune

Question 2

general categories of nonimmune causes of hemolysis

Answer 2

• physical trauma to RBC (MAHA, malignant HTN, exercise, heat, heart valve)
• antagonists (toxins, infectious agents)

Question 3

general antagonist behind the hemolysis in HUS, TTP and DIC

Answer 3

thrombi in microcirculation

Question 4

snake bites often cause mechanical damage to RBCs via…

Answer 4

DIC

Question 5

general signs of traumatic injury to RBCs on PB and in chemistry

Answer 5

• schistocytes/helmet cells
• ↑ retics/polychromasia
• striking poik
• signs of IV hemolysis (hemoglobinuria, ↓ hapto, ↑ LD, ↑ unconjugated bilirubin)

Question 6

general term indicating RBCs are lysed or damaged by microcirculatory lesions or shear forces in circulation

Answer 6

microangiopathic hemolytic anemia (MAHA)

Question 7

explain the process of MAHA

Answer 7

1. endothelial lining of small vessels damaged
2. platelets & fibrin deposits form
3. thrombus formation in vessels
4. RBCs forced through fibrin strands in thrombus, causing fragmentation

Question 8

MAHA hemolysis is (intravascular/extravascular)

Answer 8

depends on severity
less damage —EV
more damage —IV

Question 9

examples of MAHA disorders

Answer 9

• HUS
• TTP
• DIC
• malignant HTN
• disseminated cancer
• preeclampsia/eclampsia
• HELLP syndrome

Question 10

triad of HUS s/s

Answer 10

• hemolytic anemia with schistocytes
• thrombocytopenia
• acute nephropathy/renal failure

Question 11

2 groups of HUS

Answer 11

• D+HUS—diarrhea —90% cases, mostly children <5 —caused by shiga toxin
• D=HUS —no diarrhea —atypical HUS

Question 12

causes of D+HUS

Answer 12

• E. coli O157:H7
• Shigella dysenteriae serotype I

Question 13

causes of D=HUS

Answer 13

• postinfection (Spne, viruses)
• immunosuppression (chemo)
• renal/BM transplantation
• pregnancy
• OC
• toxins

Question 14

how does shiga toxin cause HUS?

Answer 14

• enters circulation through tears in colon mucosa
• damages endothelial cells in glomeruli
• platelet activation & fibrin microthrombi form
• erythrocytes are damaged & kidney loses function

Question 15

acute onset
bloody hematuria
sudden pallor
abd pain
vomiting
bloody diarrhea

Answer 15

HUS

Question 16

(TTP/HUS) has less severe CNS sx if present.

Answer 16

HUS

Question 17

Hgb in HUS

Answer 17

7-9 g/dL, some requiring transfusion

Question 18

HUS on PB

Answer 18

• normo/normo
• schistocytes, helmet cells
• spherocytes
• polychromasia
• occasional nRBCs
• left shift of leukocytosis
• platelet count low to markedly low

Question 19

HUS chemistry findings

Answer 19

• signs of IV hemolysis
• ↑ BUN, creatinine
• hypokalemia, hyponatremia
• proteinuria, hematuria, pyuria

Question 20

HUS coag tests

Answer 20

normal to slightly elevated

Question 21

plasma exchange may be indicated in —- HUS

Answer 21

D=

Question 22

new tx for HUS

Answer 22

monoclonal Ab against shiga toxin

Question 23

etiology of TTP

Answer 23

• lack of ADAMTS13 enzyme, which cleaves vWF multimers
• vWF multimers cause thrombi by attaching to endothelials and attracting platelets

Question 24

unusually large forms of vWF multimers

Answer 24

thrombotic thrombocytopenic purpura (TTP)

Question 25

2 causes of TTP

Answer 25

- familial—mutation in ADAMTS13 gene - acquired—autoAb against gene, or precipitating factors (infections, pregnancy)

Question 26

TTP age group

Answer 26

20-50

Question 27

renal function in TTP vs HUS

Answer 27

TTP—renal dysfunction, mild to mod HUS—renal failure

Question 28

TTP on PB

Answer 28

- normo/normo - ↑↑ schistocytes - polychromasia - nRBCs - leukocytosis with left shift

Question 29

typical platelet count for TTP

Answer 29

8-40, very severe

Question 30

TTP coag tests

Answer 30

usually normal or slightly abnormal

Question 31

----- must be treated, and is 90% fatal without treatment (multiorgan failure)

Answer 31

TTP

Question 32

TTP tx

Answer 32

- FFP plasma exchange - cryo - drug tx

Question 33

DIC

Answer 33

disseminated intravascular coagulation complex bleeding & clotting condition in which normal coagulation balance is altered

Question 34

common triggers of DIC

Answer 34

- bacterial sepsis - neoplasms - trauma/burns—release of tissue factor - immunologic disorders (trxn, transplant rejection) - misc—venom or drugs

Question 35

DIC coag tests

Answer 35

very abnormal prolonged PT, PTT decreased fibrinogen positive or ↑ D-dimer

Question 36

DIC tx

Answer 36

- pRBC and platelet transfusions - FFP - factor concentrates - treatment of underlying cause important not to upset coag balance, difficult to tx

Question 37

HELLP syndrome

Answer 37

complication of pregnancy Hemolysis Elevated Liver enzymes Low Platelet count

Question 38

pathogenesis of HELLP

Answer 38

unknown

Question 39

------ may be a severe form of preeclampsia

Answer 39

HELLP

Question 40

↑ liver enzymes due to sinus obstruction or liver damage

Answer 40

HELLP

Question 41

HELLP coag tests

Answer 41

usually normal

Question 42

malignant HTN is a form of ------- hemolysis with unknown mechanism

Answer 42

MAHA

Question 43

caused by artificial heart valve damage to RBCs

Answer 43

traumatic cardiac hemolytic anemia

Question 44

in this form of MAHA, platelet count is normal

Answer 44

traumatic cardiac hemolytic anemia

Question 45

Waring Blender syndrome

Answer 45

traumatic cardiac hemolytic anemia

Question 46

prominent on PB of a burn patient

Answer 46

- microspherocytes - RBC budding - schistocytes - aniso/poik

Question 47

"march hemoglobinuria"

Answer 47

excercise-induced short term

Question 48

traumatic disruption of RBCs with no anemia and no schistocytes

Answer 48

exercise-induced hemoglobinuria

Question 49

potential complication of march hemoglobinuria

Answer 49

IDA

Question 50

malaria usually causes a mild -----/------ anemia, but ----------- can cause a severe anemia

Answer 50

normo/normo Plasmodium falciparum

Question 51

malaria causes (EV/IV) hemolysis

Answer 51

both

Question 52

3 life stages of malaria

Answer 52

1. ring form 2. schizont form 3. gametocyte

Question 53

protozoan infection of RBCs looks like malaria

Answer 53

babesiosis

Question 54

coccobacillus that releases proteins inducing pitting of RBC membrane

Answer 54

bartonellosis

Question 55

GI flora that can cause rapid, massive hemolysis in bloodstream

Answer 55

Clostridium perfringens

Question 56

--------- venom cleaves off glycophorins, causing C-mediated lysis

Answer 56

brown recluse