52 Fragmentation Hemolytic Anemia

Question 1

Two-thirds of HELLP patients are diagnosed antepartum, usually between_______ weeks

Answer 1

27 and 37 weeks

The remaining third are diagnosed in the postpartum period, from a few to 48 hours after delivery (occasionally as long as 6 days).

Question 2

Risk factors for HELLP syndrome

Answer 2

• European ancestry
• Multiparity
• Maternal age (older than age 34 years), and
• A personal or familial history of the disorder

Question 3

In a preeclamptic pregnancy, the second wave fails to penetrate adequately the spiral arteries of the uterus, perhaps as a result of reduced placental expression of ______

Answer 3

Syncytin

Question 4

Functions as an antiangiogenic protein because it binds to vascular endothelial growth factor (VEGF) and placental growth factor (PGF) and prevents their interaction with endothelial cell receptors.

Answer 4

Soluble vascular endothelial growth factor receptor-1 (sVEGF receptor-1, or sVEGFR-1)

Ratio of sVEGFR-1 to PGF levels is increased.
Result is maternal glomerular endothelial cell and placental dysfunction

Question 5

Another antiangiogenic molecule that is capable of binding to and inactivating the proangiogenic growth factors, TGF-β1 and TGF-β

Answer 5

Soluble form of endoglin (sEng)

The presence of elevated serum levels of both sFLT-1 (sVEGFR-1) and sEng may be associated with the progression of preeclampsia to HELLP.

Question 6

Ninety percent of patients with HELLP syndrome present with

Answer 6

Malaise and right upper quadrant or epigastric pain

Fever is not typically seen.

Question 7

Type of LDH

The ratio of ________(an isoenzyme found specifically in the liver) to total LDH is elevated in proportion to the severity of HELLP.

Answer 7

LDH-5

Question 8

The high LDH seen in HELLP is most likely the result, principally, of ______________ rather than hemolysis

Answer 8

Liver damage

Question 9

Liver enzymes usually return to normal within _______days postpartum.

Answer 9

3–5 days postpartum

Question 10

Has been used in a classification system to predict maternal morbidity and mortality, the rapidity of postpartum recovery, the risk of disease recurrence, and perinatal outcome

Answer 10

Thrombocytopenia

BMA fonding: abundant megakaryocytes are found consistent with a consumptive thrombocytopenia causing reduction of the normal platelet lifespan of approximately 10 days to 3–5 days.

The platelet count nadir occurs 23–29 hours postpartum, with subsequent normalization within 6–days.

Question 11

Mississippi triple-class system: based on platelet count

Class 1:
Class 2:
Class 3:

Answer 11

Class 1: less than 50 × 109/L ***highest incidence of perinatal morbidity and mortality

Class 2: between 50 and 100 × 109/L

Class 3:greater than 100 × 109/L

Class 1 HELLP syndrome have the highest incidence of perinatal morbidity and mortality and have the most protracted recovery periods postpartum.

Question 12

TRUE OR FALSE

There is a indirect correlation between the extent of thrombocytopenia and measurements of liver function.

Answer 12

FALSE

There is a direct correlation between the extent of thrombocytopenia and measurements of liver function

But the same cannot be said for the severity of associated hepatic histopathologic changes.

Question 13

TRUE OR FALSE

Unlike TTP, the thrombi found in organs involved in the HELLP syndrome contain increased amounts of fibrin and low levels of VWF.

Answer 13

TRUE

Unlike TTP, the thrombi found in organs involved in the HELLP syndrome contain increased amounts of fibrin and low levels of VWF.

• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are usually within normal limits
• von Willebrand factor (VWF) antigen levels increase in proportion to the severity of the disease, reflecting the extent of endothelial damage
• No unusually large VWF multimers are present in plasma,and ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin domains-13) levels are within a broad normal range

Question 14

Seen in the last trimester or postpartum and presents with thrombocytopenia and right upper quadrant pain, but the levels of AST and ALT only rise to one to five times normal, and the PT and activated partial thromboplastin time (aPTT) are both prolonged

Answer 14

Acute fatty liver of pregnancy

Biopsy liver: fat in the cytoplasm of centrilobular hepatocytes; inflammation and patchy hepatocellular necrosis

Question 15

Indications for delivery in HELLP

Answer 15

• Severe disease presentation
• Maternal DIC
• Fetal distress
• Gestational age greater than 32 weeks with evidence of lung maturity

Question 16

TRUE OR FALSE

The use of dexamethasone has fallen out of favor after large randomized trials found that it did not reduce the duration of hospitalization, amount of blood products transfused, maternal complications, or time to normalization of laboratory abnormalities

Answer 16

TRUE

The use of dexamethasone has fallen out of favor after large randomized trials found that it did not reduce the duration of hospitalization, amount of blood products transfused, maternal complications, or time to normalization of laboratory abnormalities

Question 17

TRUE OR FALSE

Plasma exchange cannot arrest or reverse HELLP syndrome when used antepartum but may minimize hemorrhage and morbidity when used peripartum.

Answer 17

TRUE

Plasma exchange cannot arrest or reverse HELLP syndrome when used antepartum but may minimize hemorrhage and morbidity when used peripartum.

Can also be tried postpartum in the 5% of patients who fail to improve within 72–96 hours of delivery.

Question 18

Indications of liver transplantation in HELLP

Answer 18

Large hematomas or total hepatic necrosis

Question 19

Hepatic hematoma is usually present in the ____________________

Answer 19

Anterior superior portion of the right lobe of the liver

Complain of right-sided shoulder pain and are found to be in shock with ascites or pleural effusions

Emergency surgery is required for hepatic artery embolization or ligation, hepatic lobectomy, or even liver transplantation in patients with total hepatic necrosis.

Question 20

TRUE OR FALSE

One-third of all babies born to mothers with HELLP have thrombocytopenia

Answer 20

TRUE

One-third of all babies born to mothers with HELLP have thrombocytopenia

Intraventricular hemorrhage is seen very infrequently in thrombocytopenic infants
Fetal morbidity and mortality rates are each approximately 15%.

Question 21

DISSEMINATED MALIGNANCY

80% of the tumors are mucinous adenocarcinomas of either the ____________________

MAHA is more likely to be associated with metastatic malignant disease than with localized cancers or benign tumors.

Answer 21

Stomach (55%)
Breast (13%)
Lung (10%).

The median age at diagnosis is 50 years, with a slight male predominance.

Question 22

Two distinct mechanisms in Cancer-associated MAHA:

Answer 22

(a) DIC with intravascular occlusions (often partial) of small vessels by platelet-fibrin thrombi or

(b) Intravascular tumor emboli

Question 23

TRUE OR FALSE Cancer-associated MAHA:

Although the reticulocyte count can be high, it is an unreliable measure of hemolysis because extensive replacement of the marrow by metastatic tumor may prevent the reticulocytosis expected with MAHA.

Answer 23

TRUE

Although the reticulocyte count can be high, it is an unreliable measure of hemolysis because extensive replacement of the marrow by metastatic tumor may prevent the reticulocytosis expected with MAHA.

Question 24

The most common cause of anemia in malignancy is

Answer 24

Anemia of inflammation

Question 25

Autoimmune hemolytic anemia secondary to malignancy is seen in:

Answer 25

Lymphoproliferative disease

Occasionally seen with carcinoma of the stomach, colon, breast, and cervix

Question 26

Anemia was subsequently shown to be caused by erythrocyte shearing and fragmentation as the red cells traversed the turbulent flow through or around the prosthetic valve.

Answer 26

HEART VALVE HEMOLYSIS

Question 27

Factors can increase the chance of valvular hemolysis

Answer 27

• Presence of central or paravalvular regurgitation
• Placement of small valve prostheses with resultant high transvalvular pressure gradients
• Regurgitation because of bioprosthetic valve failure, seen especially when the valve is more than 10–15 years old

Question 28

A transvalvular pressure gradient of more than 50 torr can generate shearing forces exceeding 4000 dynes/cm2, more than the ___________ dynes/cm2 usually needed to cause red cell fragmentation.

Answer 28

3000 dynes/cm2

Question 29

The presenting complaint is passage of dark urine immediately after physical exertion in the upright position, occasionally accompanied by nausea, abdominal cramps, aching in the back or legs, a “stitch in the side,” or a burning feeling in the soles of the feet

Answer 29

MARCH HEMOGLOBINURIA

Anemia is uncommon
Morphologic evidence of red cell damage is not seen
Renal damage is also not commonly seen

Question 30

A syndrome that usually develops in early childhood and is characterized by thrombocytopenia, MAHA, consumptive coagulopathy, and hypofibrinogenemia caused by an enlarging kaposiform hemangioendothelioma or tufted angioma.

Answer 30

Kasabach-Merritt phenomenon