MAHA and Thrombocytopenia

Question 1

classic hematological finding on the PBS of maha

Answer 1

schistocytes. caused by damaged vascular endothelium.

Question 2

reasons behind MAHA

Answer 2

TTP, HUS, DIC, HELLP, and hypertensive crises.

Question 3

what indicate MAHA on the CBC

Answer 3

thrombocytopenia, low Hb.

Question 4

Markers of hemolysis anemia

Answer 4

increased LDH, increased bilirubin, low haptoglobin

Question 5

What must you rule out to diagnose MAHA

Answer 5

Negative DAT/coombs test which rules out autoimmune hemolysis

Question 6

TTP is caused by a deficiency of ____ needed to cleave ultralarge ____ multiverses. These multiverses aggregating can cause uncontrolled platelet agglutination.

Acquired ___ deficiency is typically due to inhibition by an ____

Answer 6

TTP is caused by a deficiency of ADAMTS13 needed to cleave ultralarge WVF multiverses. These multiverses aggregating can cause uncontrolled platelet agglutination.

Acquired deficiency is typically due to inhibition by an autoantibody.

Question 7

Primary clinical diagnosis when a patient presents with thrombocytopenia and MAHA without an alternative explanation

Answer 7

TTP

Question 8

Lab findings of TTP

Answer 8

MAHA: schistocytes
Increased LDH
Thrombocytopenia
Increased bilirubin
Decreased haptoglobin. 
Decreased ADAMTS13 activity.
PT, PTT normal

Question 9

T/F in TTP, PT and PTT are elevated

Answer 9

False. Nothing is wrong with clotting, it’s causing aggregation of VWF and platelet agglutination (factors aren’t actually doing anything).

PT/INR and PTT is normal

Question 10

treatment of TTP

Answer 10

It’s a medical emergency.

Daily plasma exchange is required, and steroids or immunosuppressive therapy is used in addition.

Question 11

Platelet transfusions are done in TTP?

Answer 11

No. Platelet transfusions are avowed in TTP and may be dangerous as it provides fuel for the development of thrombosis.

Question 12

HUS caused by ____

Answer 12

Shiga toxin, or some types of ecolI

Consider HUS if person has diarrhea and also thrombocytopenia/maha

Question 13

Just like TTP, HUS needs plasma exchange?

Answer 13

FALSE. HUS is supportive. It will go away, unlike TTP which has an inherent problem with ADAMTS13, shiga toxin might temporarily bind to ADAMTS13 to make it look like TTP but antibiotics will help

Question 14

_____ is a syndrome of unregulated systemic coagulation, which results in widespread deposition of fibrin clots in blood vessels. Results in consumption of platelets and coagulation factors, resulting in ___ ___ as well as compromised blood flow due to ____ which can ultimately lead to tissue ____ and organ damage.

Answer 14

DIC is a syndrome of unregulated systemic coagulation, which results in widespread deposition of fibrin clots in blood vessels. Results in consumption of platelets and coagulation factors, resulting in EXCESSIVE BLEEDING as well as compromised blood flow due to THROMBOSIS which can ultimately lead to tissue ISCHEMIA and organ damage.

Question 15

DIC can be considered as a 3 step process.

Answer 15

1. Release of large amounts of tissue factor stimulates the extrinsic pathway by activating
   FVII
2. Excessive thrombin production and defective physiologic anticoagulant mechanisms.
   There is a reduced production and increased consumption of antithrombin, protein C,
   protein S and tissue factor pathway inhibitor.
3. Suppression of fibrin clot degradation due to inhibition of fibrinolysis

Question 16

DIC is associated with thrombocytopenia and MAHA as well as _____ PT/INR, ____ PTT and _____ fibrinogen and ____ D-Dimer

Answer 16

DIC is associated with thrombocytopenia and MAHA as well as INCREAED PT/INR, INCREASED PTT and DECREAED fibrinogen and INCREASED D-Dimer

Question 17

HELLP REFERES TO A SYNDROME characterized by ___, ___ liver enzymes and ____ platelet count in obstetrical patients.

Answer 17

HELLP REFERES TO A SYNDROME characterized by MAHA, ELEVATED liver enzymes and DECREASED platelet count in obstetrical patients.

Question 18

T/fMAHA is immune

Answer 18

False. It’s a non-immune intravascular hemolysis. Defined by the presence of RBC fragments on peripheral blood smear.

Question 19

Name thrombotic microangiopathies vs system disorders with MAHA

Answer 19

Thrombotic microangiopathies: TTP, HUS

systemic: HELLP, DIC

Not all MAHA is caused by a thrombotic microangiopathies, but nearly all thrombotic microangiopathies cause MAHA and thrombocytopenia.

Question 20

Lab testing for MAHA

Answer 20

1. PBC— schistocytes
2. CBC— anemia (low Hb) and thrombocytopenia (decreased platelets)
3. Negative DAT (non-immune) Rules out autoimmune hemolytic anemia
4. Increased LDH (indicates hemolysis), increased total and indirect (bilirubin) (increased RBC turnover), decreased haptoglobin
5. Other testing to look for systemic disorders (ex/ DIC may have low fibrinogen and high D-Dimer)

Question 21

In HUS, is there a deficient ADAMTS13?

Answer 21

NO. It looks like there is a decreaed in ADAMTS13, but there is actually a sufficient concentration. Shiga toxin is preventing it from doing it’s job though, causing platelet agglutination.

Question 22

Compare and contrast HUS vs TTP in terms of age of onset, presence of diarrheal illness, and clinical tetrad/pentad

Answer 22

HUS: 
Age: child bc of shiga or ecolI
- present diarrhea illness
 HUS TETRAD
- MAHA
- mild/moderate thrombocytopenia
- acute kidney FAILURE
- MILD neurological symptoms
- LABS: Shiga toxin, ADAMTS13 normal

TTP”
Age; adults. No diarrheal illness

Clinical Pentad:

• MAHA
• severe thrombocytopenia
• acute kidney INJURY
• SEVERE neurological symptoms
• fever
• ADAMTS13 SEVERELY reduced, no shiga toxin

Question 23

Clinical symptoms of acute DIC and chronic DIC

Answer 23

Acute DIC: profound system bleeding (no protein C, no protein S or antithrombin), and MAHA, and Tissue ischemia/multiorgan dysfunction (because thrombin activation is through the roof at the same time, causing clots and shearing everywhere)

Chronic DIC: SPECTRUM because of continuous release of small amounts of TG. Minor mucocutaneous bleeding or arterial/venous thrombosis (VTE)

Question 24

Most common cause of chronic DIC

Answer 24

Solid tumors

Question 25

DIC treatment

Answer 25

• treat underlying cause
• if bleeding: platelet transfusion if platelets less than 50. Frozen plasma if PTT >1.5 ULN and cryoprecipitate if fibrinogen is <1.5

Question 26

T/F should use heparin for DIC to overcome clots

Answer 26

False. Higher risk of increased bleeding if heparin used in Acute DIC

Question 27

HELLP syndrom

Answer 27

Hemolysis with a microangiopathic blood smear
ELEVATED LIVER enzymes
LOW PLATELETS in obstetrical patients.