Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura: a case report and review of the literature

Case report

A 32-year-old Asian female presented to the University of Hong Kong-Shenzhen Hospital on 6 November 2021, complaining of a headache for 6 months and purpura for 3 weeks. The patient had been experiencing intermittent headaches with tinnitus for 6 months, prior to admission. Complete blood cell count (CBC) revealed a white blood cell (WBC) count of 3.07 × 109/L, hemoglobin (HGB) of 106 g/L, and platelet (PLT) count of 210 × 109/L. Brain magnetic resonance imaging (MRI) showed normal findings.

Three weeks prior to admission, the patient noticed purpura on her extremities, and she also complained of increased menstrual flow. She had received two doses of the inactivated coronavirus disease 2019 (COVID-19) vaccine in May 2021 and in June 2021. She had no history of significant medical illness, except for one stillbirth. She denied alcohol, tobacco, or drug abuse. She had never received a transfusion. She took no medications on admission, and there was no significant family medical history.

Physical examination revealed an afebrile, normotensive female. There were no hemorrhage lesions on her palate; however, multiple ecchymoses and petechiae were observed over the body. There was mild tenderness in the upper limb muscles. There was no splenomegaly, lymph node hypertrophy, or liver hypertrophy. Her physical examination was otherwise unremarkable. Chest computed tomography revealed ground-glass nodules in the left upper lung and solid nodules in the left lower lung, which were considered benign lymph nodes by radiologists. Brain MRI revealed a choroid plexus cyst. There were no significant findings from abdominal ultrasound and echocardiogram.

The urine pregnancy test was negative. CBC revealed a WBC count of 3.41 × 109/L, HGB of 77 g/L, PLT count of 28 × 109/L, mean corpuscular volume (MCV) of 96.6 fL, and vitamin B12 level of 319 pg/mL (reference: 180–914 pg/mL). Blood smear showed normal leukocyte morphology, the reticulocyte percentage was 6%, and the absolute reticulocyte count was 0.094 × 1012/L. The serum lactate dehydrogenase level was 330 U/L. The percentage of CD55− erythrocytes and CD59− erythrocytes of the total erythrocytes was less than 0.5% each. The level of glucose-6-phosphate was 23 U/L, which was normal. Thyroid function was normal, with a slightly elevated thyroglobulin antibody titer (110.3 U/mL [reference: 0–60 U/mL]). d-dimer was 1.52 µg/mL, and haptoglobin was < 25 mg/dL. Immune function test revealed IgG of 17.13 g/L complement protein 3 (C3) of 0.63 g/L. The anti-nuclear antibody (ANA) test was positive at a titer > 1:1000, with a speckled pattern. The extractable nuclear antibody profile showed strong positivity (3+) for anti-ribonucleoprotein/Smith (U1RNP/Sm) antibody. The direct Coombs’ test, anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies, antineutrophil cytoplasmic antibodies, anticardiolipin antibodies, anti-red blood cell antibodies, lupus anticoagulants, antiplatelet antibodies, and anti-β2-glycoprotein antibodies were negative. Coagulation, liver function (including bilirubin), kidney function, electrolytes, erythrocyte sedimentation rate, C-reactive protein, and iron studies were all within normal limits. Tumor markers were all negative. The urinalysis was unremarkable.

The peripheral blood smear revealed many fragmented red blood cells with increased polychromasia and decreased platelets (Fig. 1A). Bone marrow biopsy revealed relative erythroid hyperplasia and a normal megakaryocyte count (Fig. 1B). The investigations for pathogens, including human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, respiratory viruses, Epstein–Barr virus, cytomegalovirus, and Helicobacter pylori, were negative. The clinical scenario revealed Coombs’-negative hemolytic anemia, complicated with immune-mediated thrombocytopenia that was possibly caused by an autoimmune disease.

Fig. 1figure 1

A The peripheral blood smear shows schistocytes (red arrows) and reticulocytes (blue arrows) (×400). B Bone marrow megakaryocyte with increased size and platelet production deficiency (×1000)

The patient was initially treated with intravenous methylprednisolone 40 mg for 1 day, but the schistocytes in the peripheral blood increased to over 6%. The methylprednisolone dose was then increased to 240 mg for 5 days. The patient’s platelet count increased to 216 × 109/L, but the schistocytes remained at 5%. The PLASMIC score was high. The PLASMIC score is a seven-component clinical prediction tool that was developed to reliably assess the pretest probability of severe ADAMTS13 deficiency [C statistic 0.96, 95% confidence interval (CI) 0.92–0.98] [9, 10]. TTP was suspected. The ADAMTS13 activity was 1.65%, and the ADAMTS13 inhibitor assay was positive; therefore, a diagnosis of TTP was considered. The patient then received six cycles of PEX. Cyclosporine was added, and the dosage was titrated to 150 mg per day. Following treatment, the PLT count remained normal, schistocytes were reduced to 1–2%, ADAMTS13 activity increased to 63.99%, and anti-ADAMTS13 antibody was negative. During hospitalization, the patient did not present any signs of thrombosis, and all blood vessel ultrasounds were normal. She was discharged and managed in an outpatient clinic with tapered oral methylprednisolone. At the last visit, on 2 June 2022, oral methylprednisolone and cyclosporine were discontinued, and the patient only took hydroxychloroquine 0.2 g once daily. The patient’s CBC remained normal.

Systemic literature review

Sixteen publications [7,8,9, 11,12,13,14,15,16,17,18,19,20,21,22,23] were evaluated in detail, and a total of 24 patients (including our patient) were included in this qualitative analysis. The patients’ ages ranged from 9 to 72 years old, and the mean age was 36 years. There were 14 females and 10 males; 7 patients were HIV positive, 3 patients were postpartum women, 3 had autoimmune diseases (such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and Sjögren’s syndrome), 1 case was drug related, 1 patient had a history of a tumor, 1 had a positive Coombs’ test, and the remaining 8 patients had no known underlying medical conditions. The common laboratory characteristics were thrombocytopenia, elevated schistocytes, and elevated lactate dehydrogenase (LDH). Only 6 patients’ ADAMTS13 activity was detected (ranging from 0% to normal). The most common symptoms were mucocutaneous bleeding (n = 16), neurological symptoms (n = 16), and fever (n = 14). All patients received PEX and/or steroids. Intravenous immunoglobulin, splenectomy, vincristine, and rituximab were the most common assistant therapies. Following treatment, 20 patients were in remission, and 4 patients (16.7%) died. The results are presented in Table 1.

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