This document discusses microangiopathic hemolytic anemia (MAHA) and thrombotic thrombocytopenic purpura (TTP). It recommends ordering tests like LDH, haptoglobin, reticulocyte count, and ADAMTS13 level if MAHA is suspected. ADAMTS13 levels below 10% are specific for TTP, caused by acquired or hereditary deficiencies of the von Willebrand factor cleaving protease ADAMTS13. Initial treatment for suspected TTP includes plasma exchange while waiting for test results. Differential diagnoses are discussed including thrombotic microangiopathies, autoimmune hemolytic anemia, immune thrombocytopenic purpura, and aplastic

1.  What is MAHA?
 Thrombocytopenia from platelet consumption, erythrocyte fragmentation and hemolysis are
due to mechanical injury of the red blood cells by abnormal levels of shear stress.

2.  Look for AST on the CMP
 Ask the ER to order reticulocyte count, LDH and haptoglobin (maybe DAT later)
 Request the lab to prepare a peripheral blood smear
 Consult hematology

3. ©2017 UpToDate®
If I see the above with a high LDH and low haptoglobin, I go ahead and order ADAMTS13 level

4. Conditions that result in MAHA(other than mechanical devices)
Wintrobe’s Clinical Hematology 13th edition

6.  Acquired: autoimmune inhibitors of ADAMTS13 (A Disintegrin And Metalloprotease
with a ThromboSpondin type 1 motif, member 13)
 Von Willebrand factor cleaving protease
 Hereditary: mutations of ADAMTS13

7. Moake J. Clin Transl Sci. 2009 Oct;2(5):366-73

8. Interaction between ADAMTS13, vWF and Platelets
Wintrobe’s Clinical Hematology 13th edition

9. ©2017 UpToDate®

10. Progression of TTP complications
Wintrobe’s Clinical Hematology 13th edition

11.  Send off an ADAMTS13 level- 2 blue top tubes
 Arrange for TPE

12.  Hemolytic uremic syndrome- Shiga toxin-producing E. coli (O157:H7 and O104:H4) or
Shigella dysenteriae
 No GI illness, Renal failure<<<<Neuro issues
 How about aHUS?

13.  A: Idiopathic aHUS
 - Mutations or genetic variants of CHF, MCP, CFI, CFB, C3, THBD, etc.
 - Autoantibodies to CFH, with or without CFHR1 genomic deletion
 B: Co-morbidity as a trigger of aHUS presentation in patients with the disease
 - Pregnancy, IV contrast, pancreatitis, infection, inflammation, surgery, trauma, etc.
 C: Co-morbidity causing defective complement regulation (e.g., CFH autoantibodies)
 - Hematopoietic stem cell therapy
 - Suspected, but not yet proven: HIV infection, systemic autoimmune diseases,
drugs, etc.

14.  Send off ADAMT13 testing and STEC testing
 If platelets >30,000 and Creatinine >2, it is less likely to be TTP
 Testing might take a few days to come back, so in the meantime start TPE
 ADAMTS >10% rules out TTP (do not get confused with normal ranges)
 HUS would need supportive management
 aHUS- treat with Eculizumab (anti C5 inhibitor)

15.  Less likely given the disconnect between the severity of thrombocytopenia and the
patient’s clinical presentation
 Would need PT, PTT, Fibrinogen and D-dimer

17.  Evans syndrome- AIHA and ITP
 AIHA can be warm-IgG mediated or Cold-IgM mediated
 If the smear does not show schistocytes but instead shows spherocytes or red
cell agglutination
 LDH high and hapto low
 Get a DAT
 We only see hemoglobinuria in Cold AIHA

18. Immune thrombocytopenic purpura (ITP) causing severe thrombocytopenia and subsequent anemia

19. Anti-platelet antibody induced destruction of platelets in ITP
Wintrobe's Clinical Hematology, 12th
edition

20.  Cannot explain neuro symptoms
 Cannot explain hemoglobinuria

21. Common non-autoimmune causes of thrombocytopenia in adults
Hematology Am Soc Hematol Educ Program. 2010;2010:377-84

22.  Review of peripheral smear would give us an answer along with the LDH and
haptoglobin
 Would expect petechiae or purpura with severe thrombocytopenia in leukemia

24. Bone marrow in Aplastic anemia

25. Hoffman: Hematology: Basic Principles and Practice, 5th ed

26. Differential diagnosis with pancytopenia and hypocellular marrow
Wintrobe's Clinical Hematology, 12th edition

27. Hoffman: Hematology: Basic Principles and Practice, 5th ed
Diagnostic Algorithm in Aplastic Anemia

28.  Peripheral blood smear review
 LDH, Haptoglobin, reticulocyte count
 ADAMTS13 testing

29. • PRACTICAL TIDBITS:
• Blue top specimen
• Must be drawn prior to cryoprecipitate or plasma infusion
• If a sample has been drawn, the test can be added on to specimen in lab
• If in lab by 3pm, results will be available the following evening
• ADAMTS FACTS:
• <10% is specific for patients with immune mediated or congenital TTP
• ADAMTS can be mildly-moderately decreased with inflammation, hepatic
dysfunction and pregnancy
• If ADAMTS activity is <30%, the inhibitor assay is performed