Abstract Number: PB0877
Meeting: ISTH 2021 Congress
Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » Non HUS/TTP Microangiopathies
Background: Vitamin B12 (cobalamin) deficiency, defined as a serum cobalamin level < 200 pg/mL, is a common problem. Most clinicians are aware that cobalamin deficiency causes megaloblastic anemia, hypersegmented neutrophils, and subacute combined degeneration of the dorsal spinal column. However, many general clinicians are unaware that cobalamin deficiency can cause pseudo-thrombotic microangiopathy (TMA). Psuedo-TMA presents similarly to the life-threatening condition thrombotic thrombocytopenic purpura (TTP), with laboratory evidence of hemolytic anemia. However, it is distinguished from TTP by very high levels of lactate dehydrogenase (LDH) and reticulocytopenia. Due to the extraordinarily high mortality rate of untreated TTP and its overlap in presentation with pseudo-TMA, pseudo-TMA is often treated with plasmapheresis, when simple vitamin replacement is what’s needed.
Aims: We present 3 cases of pseudo-TMA secondary to cobalamin deficiency. Our case series is important because although this pathology is known, it is not widely taught in basic medical education, leading to incorrect treatment with expensive and risky plasmapheresis.
Methods:
| Case 1 | Case 2 | Case 3 |
| 90 year old female with fatigue, weakness, anorexia, and lethargy. Found to have pernicious anemia with an intrinsic factor 100 times the upper limit of normal. Treated with 5 days of IM cyanocobalamin 1000 mcg, followed by daily sublingual tablets for life.
***[It is important to note that ALL 3 cases had complete resolution of symptoms, with near normal labs on 3 month follow up after vitamin B12 replacement.] |
32 year old male with shortness of breath for two weeks. TTP incorrectly diagnosed, so he had urgent plasmapheresis. He developed hives from the procedure, and it was stopped. Found to have severe B12 deficiency, and received 4 days of IM cyanocobalamin 1000 mcg, followed by daily sublingual tablets for life. | A 35 year old male with a history of alcohol abuse had fatigue, fevers, chills, and diarrhea. He had resolution of his GI symptoms, but persistent fatigue so he sought medical attention. Found to have severe macrocytic anemia and markedly elevated anti-parietal and anti-intrinsic antibodies. He received 5 days of IM cyanocobalamin 1000 mcg, followed by monthly injections. |
Results:
| PERTINENT LABS | Case 1 Presentation | Case 1 Discharge | Case 2 Presentation | Case 2 Discharge | Case 3 Presentation | Case 3 Discharge |
|---|---|---|---|---|---|---|
| Hemglobin (g/dL) | 3.6 | 9.5 | 5.7 | 8.4 | 6.4 | 8.3 |
| Platelets (10×3/mm3) | 50 | 104 | 82 | 76 | 187 | 114 |
| MCV (HI) | 104.9 | 91.9 | 108.8 | 100.2 | 125.7 | 108.6 |
| LDH (units/L) | 2,032 | 596 | 3,352 | 711 | 5,622 | 3,163 |
| Haptoglobin (mg/dL) | <15 | 27 | < 15 | 44 | < 15 | < 15 |
| Reticulocyte Index (RI) | 0.48 | 2.0 | 1.0 | 1.04 | 0.59 | 3.4 |
| ADAMTS 13 | > 50% | N/A | 77.1% | N/A | 73% | N/A |
| Cobalamin (pg/mL) | < 50 | > 1,500 | < 50 | 2,079 | < 50 | 1,918 |
| Peripheral Smear | Anisocytosis, poikilocytes, 1+ schisto-cytes, polychromasia, slight burr cells, hypersegmented neutrophils, rouleaux, slight basophilic stripling | No schistocytes | 1+ schistocytes, 3+ anisocytosis, 1+ macrocytes, tear drop cells, occasional ovalocytes, and hypochromia | No schistocytes | 4-5 schistocytes per HPF, anisocytosis, elliptocytosis, macrocytosis, thrombocytopenia, hypersegmented neutrophils, no inclusion bodies noted | 1+ schistocytes, polychromasia, anisocytosis, poikilocytes, 1+ macrocytes, and occasional burr cells, teardrop cells, and ovalocytes. |
Conclusions: All three cases had the following similarities: schistocytes, undetectable haptoglobin, thrombocytopenia, normal renal function, significantly high levels of LDH (>2000 IU/L), and recitulocytopenia, with a low reticulocyte index (RI <2). These findings highlight how difficult it can be to distinguish TTP from psudeo-TMA, but also feature differences. The high LDH and low RI can be explained from a hypo-proliferative bone marrow response from insufficient cobalamin levels. None of the patients had a low ADAMTS13 level, nearly excluding TTP since ADAMTS13 activity less than 10% is a relatively specific finding in TTP. The risk of an adverse event in plasmapheresis is nearly 30%, and the cost exceeds $100,000 in the setting of TTP. This unnecessary risk and enormous financial burden can be eliminated if replacement of cobalamin is given in a timely manner. Our hope is that this case series prevents erroneous treatment in the future.
To cite this abstract in AMA style:
Jones C, Kumar R. Vitamin B-12 Deficiency and Pseudo Thrombotic Microangiopathy: A Case Series [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/vitamin-b-12-deficiency-and-pseudo-thrombotic-microangiopathy-a-case-series/. Accessed December 5, 2021.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/vitamin-b-12-deficiency-and-pseudo-thrombotic-microangiopathy-a-case-series/