Here we present a case of a 39-year-old female with the chief complaints of syncopal episodes, blurred vision associated with headaches, generalized abdominal pain, and hypertensive emergencies. The patient was known for chronic hypertension medically managed with a combination of hydrochlorothiazide and valsartan, iron deficiency secondary to the fibroid, and the episode of provoked deep vein thrombosis and pulmonary embolism with a negative work-up on thrombophilia. The patient was also taking Vitamin D and Vitamin C supplements. Tenderness on palpation was noted over the whole abdomen, along with blurred vision in both eyes with a patch test on a physical examination.
The laboratory investigations at that point revealed a low hemoglobin count of 9.8 mg/dl, low platelet in the range of 52,000 per microliter, low potassium of 3 mEq/L, high levels of creatinine (Cr) 6.7 mg/dl with increased blood urea nitrogen (BUN) levels of 59 mg/dl. Due to clinical triads such as thrombocytopenia, hemolysis pattern, and neurological manifestation, we ordered ADAMTS-13 level. On her thrombophilia work-up, haptoglobin was less than 20 mg/dl, with an LDH of 752 U/L and an average ADAMTS13 level. The PLASMIC score, which predicts ADAMTS13 deficiency in patients with suspected thrombotic thrombocytopenic purpura (TTP), was 5, suggesting moderate risk. With high levels of abnormal creatinine levels and BUN, renal biopsy was done to look for the cause of acute kidney injury in the setting of suspected TTP, which revealed diffuse thrombotic microangiopathy, along with moderate to chronic changes with greater than 50% tubular atrophy and interstitial fibrosis. CT scan of the brain was negative for detecting any cause of syncope. However, MRI showed lacunar infarcts secondary to thromboembolism.
A provisional diagnosis of TTP with an average ADAMTS13 level was made, and the patient was started on plasma exchange. Drastic improvement in the symptoms was noted with FFP and eight units of plasma exchange.
ADAMTS 13 is a critical enzyme responsible for dividing the multimers of the von Willebrand factor. The ADAMTS13 level of less than 10% or less has a sensitivity value of 97% and a specificity value of 100% to diagnose TTP in suspected individuals [2]. Despite that, some patients whose clinical presentations are consistent with TTP but whose lab work shows normal levels.
Despite average enzyme level, inhibitory acquired autoantibodies to ADAMTS13 called acquired TTP usually block the enzyme’s ability to divide the multimers. An alternate explanation could be genetic alteration and mutations in the ADAMTS13 enzyme, which leads to the loss of the enzyme’s functional capacity[9]. For some patients who receive plasma exchange therapy, redistribution of anti-ADAMTS antibodies between intra and extravascular space leads to fast neutralization of infused plasma ADAMTS13 levels [10]. In these cases, patients can be found as usual or mild to decrease ADAMTS13 level [11].
TTP diagnosis could be challenging based on the enzyme level and one must carefully evaluate the clinical presentation, laboratory, and imaging findings and apply the prediction score like PLASMIC after ruling out other possible alternative diagnoses. Timely and appropriate treatment of TTP, regardless of ADAMTS level, is essential as it can significantly decrease the risk of complications and improve overall prognosis.
Our case is a rare presentation of acquired TTP where ADAMTS13 levels were found to be normal. As TTP may eventually cause severe renal, neurological complications, mucocutaneous bleeding, or intravascular bleeding, it is important to look at the clinical presentation with a triad of thrombocytopenia, hemolysis patterns, and neurological presentation even with normal ADAMTS13 levels in an elderly population.