TMA 2

Question 1

Patient presents with fever, hemolytic anemia, Cr is 3.1 (baseline is normal), platelet count is 90. Vitals significant for BP 180/89. What is diagnosis and initial treatment?

Answer 1

atypical HUS
Eculizumab

Question 2

Patient presents with new thrombocytopenia, hemolytic anemia, confusion. Platelets are 15k. Does not have any renal impairment. Vitals are normal. What is the diagnosis and initial treatment?

Answer 2

TTP
PLEX

Question 3

Describe pathophysiology of TTP

Answer 3

ADAMTS13 is a protein that normally snips the long vWF multimers into smaller pieces that can circulate without problem. In ADAMTS13 deficient state, these long vWF multimers circulate, bind platelets and cause aggregation, causing microthrombi in small vessels. Thrombocytopenia results because platelets are used up in the microthrombi

Question 4

What are three clinical features that can distinguish aHUS from TTP

Answer 4

TTP has more severe thrombocytopenia (<30k)
aHUS has more significant renal impairment and more frequently has new/severe HTN

Question 5

Four risk factors for TTP relapse

Answer 5

Black
Male
Lower ADAMTS13 level (<20% by 30 days)
Non-O blood type

Question 6

What is an option for patients with congenital TTP who have mild symptoms that is not an option for those with acquired TTP?

Answer 6

Plasma infusion. They don’t have an inhibitor to ADAMTS13, so they don’t need plasmapheresis

Question 7

In treatment of TTP, how long to you continue PLEX?

Answer 7

Until normal platelet count for 2 days

Question 8

Indication for Caplacizumab in acute, initial presentation of TTP?

Answer 8

Those who are critically ill with neurologic issues or with high troponin

Question 9

INitial treatment for TTP

Answer 9

PLEX and Rituximab +/- caplacizumab

Question 10

Mechanism of action of Caplacizumab

Answer 10

Antibody that binds to A1 domain of VWF, blocking VWF-platelet interaction

Question 11

Side effect of caplacizumab

Answer 11

Mucocutaneous bleeding (typically mild)

Question 12

Management of refractory TTP

Answer 12

Start caplacizumab
Intensify immunosuppression (Add Ritux if not already on it). Can add CSA

Question 13

Describe pathogenesis of atypical HUS

Answer 13

Patients with certain mutation that cause imbalance of activating and inhibitory complement proteins are at high risk. These patients then experience some trigger (infection, surgery, pregnancy, autoimmunity), causing uncontrolled complement activation causing endothelial injury, platelet aggregation, and microthrombi

Question 14

Mechanism of action of Eculizumab

Answer 14

Anti-C5 monoclonal antibody

Question 15

What is significant infectious side effect of eculizumab? and how to manage it?

Answer 15

Increased risk of meningococcal infection. If not vaccinated, need short course prophy antibiotics

Question 16

How long do you continue eculizumab in aHUS?

Answer 16

Until trigger resolves, TMA has resolved, and renal function is normal or at new baseline

Question 17

What is the clinical benefit seen in Eculizumab when treating aHUS

Answer 17

Improves platelet count in 7-10 days
Improves renal function after weeks

Question 18

Mechanism of ravulizumab

Answer 18

Long-acting C5 inhibitor

Question 19

Patient is admitted to the ICU with fever, mild thrombocytopenia, mildly prolonged PT/PTT. He has some oozing from IV sites. What is most likely diagnosis and treatment?

Answer 19

DIC
Cryoprecipitate to keep PT <2 and Fib >150