A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome

Bernard-Soulier syndrome (BSS) is a rare inherited disorder characterized by unusually large platelets, low platelet count, and prolonged bleeding time. BSS is usually inherited in an autosomal recessive (AR) mode of inheritance due to a deficiency of the GPIb-IX-V complex also known as the von Willebrand factor (VWF) receptor. We investigated a family with macrothrombocytopenia, a mild bleeding tendency, slightly lowered platelet aggregation tests, and suspected autosomal dominant (AD) inheritance. We have detected a heterozygous GP1BA likely pathogenic variant, causing monoallelic BSS. A germline GP1BA gene variant (NM_000173:c.98G > A:p.C33Y), segregating with the macrothrombocytopenia, was detected by whole-exome sequencing. In silico analysis of the protein structure of the novel GPIbα variant revealed a potential structural defect, which could impact proper protein folding and subsequent binding to VWF. Flow cytometry, immunoblot, and electron microscopy demonstrated further differences between p.C33Y GP1BA carriers and healthy controls. Here, we provide a detailed insight into its clinical presentation and phenotype. Moreover, the here described case first presents an mBSS patient with two previous ischemic strokes.

Clinical impact of glycans in platelet and megakaryocyte biology

Humans produce and remove 1011 platelets daily to maintain a steady-state platelet count. The production of platelets by bone marrow megakaryocytes and their removal from the blood circulation are tightly regulated mechanisms, and abnormalities in both processes can result in thrombocytopenia (low platelet count) or thrombocytosis (high platelet count), often associated with the risk of bleeding or overt thrombus formation, respectively. This review focuses on the role of glycans, also known as carbohydrates or oligosaccharides, including N- and O-glycans, proteoglycans, and glycosaminoglycans, in human and mouse platelet and megakaryocyte physiology. Based on recent clinical observations and mouse models, we focused on the pathological aspects of glycan biosynthesis and degradation and its effects on platelet numbers and megakaryocyte function.

Platelet Count and Volume and Pharmacological Closure with Paracetamol of Ductus Arteriosus in Preterm Infants

Background: Low platelet count might promote resistance to pharmacological closure with indomethacin and ibuprofen of a hemodynamically significant patent ductus arteriosus (hsPDA). However, no studies have investigated if this occurs with paracetamol. Methods: We retrospectively assessed the correlation between platelet count, mean platelet volume (MPV), and plateletcrit (PCT), as well as the effectiveness of paracetamol in closing hsPDA in infants born at 23+0–31+6 weeks of gestation who were treated with 15 mg/kg/6 h of i.v. paracetamol for 3 days. Results: We studied 79 infants: 37 (47%) Had closure after a course of paracetamol and 42 (53%) did not. Platelet count and PCT did not correlate with paracetamol success or failure in closing hsPDA, while MPV was lower at birth (10.7 ± 1.4 vs. 9.5 ± 1.1; p < 0.001) and prior to starting therapy (11.7 ± 1.9 vs. 11.0 ± 1.6; p = 0.079) in refractory infants. Regression analysis confirmed that the low MVP measured prior to starting the treatment increased the risk of hsPDA paracetamol closure failure (OR 1.664, 95% CI 1.153–2.401). Conclusions: The greater MPV correlated positively with the effectiveness of paracetamol in closing hsPDA, while platelet count and PCT did not influence closure rates. Additional studies are needed to confirm our results.

A Case Study Using Papaya Leaf Extract to Reverse Chemotherapy-Induced Thrombocytopenia in a GBM Patient

Chemotherapy-induced thrombocytopenia (CIT) is a critical condition in which platelet counts are abnormally reduced following the administration of chemotherapeutic compounds. CIT poses a treatment conundrum to clinicians given the increased risk of spontaneous bleeding, obstacles to surgical management of tumors, and exclusion from clinical trials. Treatment of CIT involves the removal of the offending agent combined with platelet infusion or thrombopoietin agonist treatment. However, due to the autoimmune and infection risks associated with infusions, this treatment is only reserved for patients with critically low platelet counts. One potential solution for patients in the mid to low platelet count range is Carica papaya leaf extract (CPLE). In this case, we report the novel use of CPLE as a method of bolstering platelet counts in a patient presenting with CIT. The patient was initiated on CPLE therapy consisting of 1 tablespoon twice daily with meals. Following CPLE treatment, the patient’s platelet counts rebounded from less than 10,000/µL to 113,000/µL. This clinical vignette supports the use of CPLE in the clinical context of CIT when thrombopoietin agonists are not a viable option. The potential benefits of CPLE as a method for increasing platelet count deserve further exploration, especially as a treatment option for refractory patients or those ill-suited for other traditional thrombocytopenia therapies.

Pregnancy onset congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) mimicking HELLP syndrome: a case report

Objective Thrombotic thrombocytopenic purpura is a thrombotic microangiopathic condition characterized by hemolytic anemia, thrombocytopenia, neurologic abnormalities, fever and renal dysfunction. Thrombotic microangiopathies such as preeclampsia and HELLP syndrome are pregnancy-specific, whereas others such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome are not. In this report, we present a case at which we identified a novel mutation which led to a significant reduction of ADAMTS13 activity. Case(s) A nulliparous pregnant woman of 32-year-old presenting with epigastric pain, hypertension and low platelet count was first suspected of HELLP syndrome, but was diagnosed with congenital TTP after delivery. Conclusion HELLP syndrome co-existed with undiagnosed TTP in this case. We strive to have sufficient awareness in order to distinguish these two pathologies from each other on an antenatal basis, because the causes of the managements are entirely different.

A full-term pregnant woman with secondary Evans syndrome caused by severe coronavirus disease 2019: a case report

Background In this report, we describe a very challenging case of a patient with secondary Evans syndrome caused by severe coronavirus disease 2019 infection in a pregnant full-term woman. Case presentation A 29-year-old full-term pregnant Indonesian woman presented with gross hematuria, dry cough, fever, dyspnea, nausea, anosmia, and fatigue 5 days after confirmation of coronavirus disease 2019 infection. Laboratory examinations showed very severe thrombocytopenia, increased indirect bilirubin, and a positive direct Coombs’ test. From peripheral blood, there was an increased number of spherocytes, which indicated an autoimmune hemolytic process. Antinuclear antibody and anti-double-stranded DNA test results were negative, and her virology serological markers are also negative for human immunodeficiency virus, cytomegalovirus, and hepatitis B and C. Despite aggressive treatment with platelet transfusion, high-dose steroid, and thrombopoietin receptor agonists, the platelet count did not recover, and a speculative cesarean delivery had to be done with a very low platelet count.

First diagnosis of thrombotic thrombocytopenic purpura after SARS-CoV-2 vaccine – case report

Background We report a case of a 25-year-old male patient, who developed acquired thrombotic thrombocytopenic purpura (aTTP) after receiving a first dose of mRNA-based SARS-CoV-2 vaccine Spikevax (mRNA-1273, Moderna Biotech, USA). While this is the first case in literature describing a case of aTTP after receiving the Spikevax vaccine, there are two other cases after mRNA-based Covid-19 vaccine and two after adenoviral SARS-CoV-2 vaccine. Case presentation The patient presented with persisting malaise, fever, headache, word-finding difficulties, nausea, vomiting, petechial bleeding, and hematuria 13 days after receiving a first dose of vaccination. Laboratory testing showed low platelet count, Coombs-negative hemolytic anemia, and mild acute kidney injury. We excluded vaccine induced immune thrombotic thrombocytopenia (VITT) as another important differential diagnosis and the final diagnosis was established after ADAMTS-13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) activity was found to be < 1% (reference range > 40%) and ADAMTS-13 antibodies being 72.2 IU/L (reference range < 12 IU/L). We initiated empiric therapy of plasmapheresis and corticosteroids on admission and started caplacizumab the day after. The patient’s thrombocyte count normalized 3 days after admission, hemolysis and acute kidney injury resolved after 2 weeks. The patient received 2 doses of rituximab (1 g each) after the diagnosis of immune TTP was established. One month after the initial presentation, the patient is in good overall condition, but still receives daily caplacizumab due to ADAMTS-13 activity of < 1%. Conclusions Low platelet count after vaccination against SARS-CoV-2 has gained attraction after vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described as a rare but severe complication of adenoviral-based vaccines. Thrombotic thrombocytopenic purpura (TTP) is an important differential diagnosis, but there are only few reports of TTP following SARS-CoV-2 vaccination. Despite pathophysiological and clinical differences of both entities, diagnostic uncertainty can result in the acute setting, since they share main symptoms such as headache and neurological alterations in addition to thrombocytopenia. In difference to other cases reported, this patient developed first symptoms of TTP as early as 4 days after vaccination, which suggests that vaccination merely acted as trigger for occult TTP, instead of truly inducing an autoimmunological process.

Type 2B von Willebrand Disease: Early Manifestation as Neonatal Thrombocytopenia

Here, we report about a preterm female newborn with a prolonged course of severe thrombocytopenia and hematomas. The family history was positive for von Willebrand disease type 2B (VWD 2B). Diagnosis of VWD 2B was identified analyzing von Willebrand factor (VWF) parameters (VWF:antigen, VWF:activity, VWF multimer analyses) and performing light transmission aggregometry (with half concentration of ristocetin). In addition, the diagnosis was confirmed by molecular genetic analysis: identification of a disease-causing missense mutation (Val1316Met) in the VWF gene associated with a severe course of VWD 2B, which had been previously reported. Treatment with a VWF-containing plasma concentrate was initiated. Because the combination of prematurity and very low platelet count is often associated with intracranial bleeding, at the beginning platelet concentrates were transfused. Fortunately, the patient did not develop serious bleeding episodes. Interestingly, the patient had a mutation in the VWF gene, which had been described to be associated with aggravation of thrombocytopenia especially in stressful situations. Therefore, we replaced venous blood withdrawals by capillary blood samplings when possible and, consequently, we observed an increase of the platelet count after this change in management. At the age of 2 months, the patient was discharged after stabilization of the platelet count without any bleeding signs and without a need of long-term medication.

Partial HELLP syndrome: case report

HELLP syndrome is a complication in pregnancy clustered by haemolysis, elevated liver enzymes, and a low platelet count. It is seen as a serious complication of preeclampsia and eclampsia. Serious manifestations like haemorrhage, infarction, rupture and other hepatic manifestations are usually associated with it. In this case study, 29 years old primigravida is a booked case admitted in ward at 39 weeks 1 day with decreased fetal movement for 2 days. No history of pain abdomen, bleeding per vaginum, discharge per vaginum. Her blood pressure records at the time of admission was 110/72 mmHg and she was normotensive throughout pregnancy. Urine routine examination was negative for urinary protein. However, blood tests showed platelet count of 66,1000/cumm, with ALT of 174 U/L and AST of 123 U/L on peripheral blood film. RBC were predominantly normocytic, normochromic with few macrocytes. WBC has normal morphology. Platelets were reduced on smear. Giant platelets were seen. Ursodeoxycholic acid 300 mg 12 hourly were given to the patient and 3 doses of vitamin K I/M 24 hourly. She was delivered by cesarean section which was performed due to failure of progression of labor with a deflexed head. There was presence of retroplacental clot of 4×3 cm indicating placental abruption, a complication of HELLP syndrome. From this we conclude that we should be careful in suspecting complications of full blown diseases even when the patients are asymptomatic but have atypical laboratory findings.

Severe megaloblastic anemia in twin pregnancy mimicking partial hemolysis, elevated liver enzymes and low platelet count syndrome: a case report

Vitamin B12 is well known cause of megaloblastic anemia. However, it is uncommon in pregnancy, occurs in 10-28% of uncomplicated pregnancies, and is associated with few complications. Present case of 32 years old woman with twin-pregnancy at late gestation who was diagnosed with severe anemia in a local private clinic. On arrival to medical center, lab findings together with her clinical picture warranted the concern for differential diagnosis of partial hemolysis, elevated liver enzymes and low platelet count (HELLP), but later it was found to be a case of vitamin B12 deficiency since additional lab findings. Blood transfusions were given, and patient responded well to B12 supplementation. Pregnancy was carried to term and delivered twin live babies but otherwise well at birth and had normal developmental milestones thereafter. Our case emphasizes the importance of screening for B12 deficiency in pregnancy, especially in at-risk women (twin-pregnancy in pure vegetarian women) with unexplained anemia/r thrombocytopenia.