African horse sickness (AHS), caused by the vector-borne African horse sickness virus (AHSV), is endemic to sub-Saharan Africa and infection results in high mortality in naïve equine populations. Clinical signs include submucosal petechiae and prolonged bleeding post venepuncture indicative of hypocoagulation. Pathological activation of haemostasis may result from tissue factor expression as a result of vascular endothelial damage or dysfunction, the proposed pathologic mechanism in AHS, potentially resulting in disseminated intravascular coagulation (DIC). To describe haemostatic changes during experimental AHSV infection and to characterise DIC using plasma-based and viscoelastic assays. In vivo experiments. Four horses were experimentally infected with AHSV. Blood samples were obtained before infection, then every 24 h until humane euthanasia. Haematology and thromboelastography (TEG) were performed and prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer concentrations, as well as activities of antithrombin (AT) and coagulation factors II, VII, VIII, X, and XII were measured. Over the disease course, TEG variables showed increased clot initiation time (R) and decreased α-angle, maximum amplitude (MA), and clot strength (G). The velocity curve showed decreased maximum rate of thrombus generation (MRTG) and thrombus generation (TG), and increased time to maximum rate of thrombus generation (TMRTG). Prothrombin time, aPTT and D-dimer concentration increased while AT activity decreased. All horses developed severe thrombocytopenia. Horses experimentally infected with AHSV developed a consumptive coagulopathy with a bleeding phenotype. These findings fulfil the criteria of overt DIC characterised by procoagulant activation, inhibitor consumption and increased fibrinolytic activity.

Abstract Background: Cancer therapy-induced thrombocytopenia (CTIT) is a common complication of anti-tumor therapy and causes treatment delays or interruptions, increased bleeding risk and compromised outcomes. We aimed to evaluate hetrombopag, an oral thrombopoietin receptor agonist that prevented CTIT in breast cancer patients. Methods: In this multi-center, prospective exploratory trial (NCT05394285), breast cancer patients with platelet counts (PLT) < 50×109/L during current anti-tumor treatment cycle (Cycle 1) were enrolled. Those patients were randomized to receive either hetrombopag (7.5 mg daily, n = 30) or subcutaneous recombinant human thrombopoietin (rhTPO, 15000 U daily, n = 30) until their PLT >100×109/L, which was defined as the thrombocytopenia treatment phase (TTP). Eligible patients were scheduled to continue the same anti-tumor regimen in their subsequent treatment cycle (Cycle 2). The secondary prevention phase (SPP) was initiated using a self-controlled design, with prophylactic hetrombopag (7.5 mg/day for 14 days) administration beginning one day after the start of Cycle 2. The primary endpoint was the response rate during the SPP, defined as the proportion of patients meeting all predefined criteria before the next treatment cycle (Cycle 3): 1. no platelet transfusion requirement; 2. no anti-tumor treatment modification (≥20% dose cut, ≥5 days delay, or discontinuation) ; 3. absence of severe thrombocytopenia (PLT <25×109/L, or PLT <50×109/L for ≥7 days). Results: Between Sep 2022 and May 2025, 67 breast cancer patients were enrolled in the study. After excluding 1 patient who withdrew informed consent, 66 patients comprised the full analysis set (FAS). During the trial, 6 patients discontinued participation in the SPP, the remaining 60 patients completed both TTP and SPP, forming the per-protocol (PP) population. In the FAS, 51 (77.3%) patients received antibody-drug conjugates (ADCs) monotherapy, 14 (21.2%) received regimens containing chemotherapy (RCC), and 1 (1.5%) with targeted therapy plus ADC. In the PP population, the response rate in the SPP was 85.0% (51/60). During the TTP, 86.7% (26/30) of patients in the hetrombopag group achieved response, compared to 80% (24/30) in the rhTPO group. No treatment-emergent severe adverse events occurred. Conclusions: As the first prospective trial to evaluate hetrombopag for preventing CTIT in breast cancer patients, this self-controlled exploratory study demonstrated hetrombopag may be a promising option for the secondary prevention of CTIT. The promising response rate observed during the TPP, coupled with a favorable safety profile, supports further large-scale investigation of hetrombopag for the prevention of CTIT in multi-cycle anticancer regimens. Citation Format: H. Sun, H. Lv, W. Chen, Y. Zhao, M. Zhang, L. Niu, Z. Liu, X. Guo, X. Chen, Y. Feng, L. Wang, H. Zeng, J. Wang, Y. Cui, M. Yan. Secondary prevention of cancer therapy-induced thrombocytopenia with hetrombopag in breast cancer: a prospective,multi-center,self-controlled exploratory trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-03-01.

Concomitant pulmonary embolism and severe thrombocytopenia associated with an APS-like autoimmune thrombophilic condition: a case report.

Thrombotic thrombocytopenic purpura following one anastomosis gastric bypass surgery: a rare case report

Venous thromboembolism presents a critical complication in hematologic malignancies, profoundly affecting patient outcomes. Traditional anticoagulant options, low-molecular-weight heparin and vitamin K antagonists, encounter significant limitations, especially concerning bleeding risks exacerbated by chemotherapy-induced thrombocytopenia. Direct oral anticoagulants (DOACs), including factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) and thrombin inhibitors (dabigatran), have emerged as appealing alternatives due to their ease of use, predictable pharmacokinetics, and reduced monitoring requirements. However, their safety and optimal use remain uncertain in hematologic malignancies due to underrepresentation in clinical trials and specific bleeding risks. This review comprehensively summarizes current evidence regarding DOAC safety, efficacy, and clinical management considerations in leukemia, lymphoma, multiple myeloma, and myeloproliferative neoplasms. It emphasizes individualized anticoagulation strategies, highlights existing evidence gaps, and outlines future research priorities, particularly the safe application of DOACs in severe thrombocytopenia and interactions with targeted therapies. Ultimately, tailored anticoagulant approaches are essential to optimizing patient outcomes in this complex patient population.

Malaria is a disease which is caused by the intraerythrocytic protozoa of the genus Plasmodium. The symptoms of severe malaria include various organs damage with raised parasitemia levels, and severe metabolic acidosis. Pakistan is one of the Southeast Asian nations where malaria is endemic. Some malaria cases will progress to a serious stage. We have reported a severe case of Malaria in 50 years old male patients who develop high grade fever, chills, anemia, severe thrombocytopenia. He was treated with platelet transfusion and Cefuroxime. Unfortunately, the patient died due to Disseminated Intravascular Coagulation.

ABSTRACTTransient severe neutropenia and thrombocytopenia are frequent during treatment of hematological malignancies and contribute to early mortality through sepsis and bleeding. While neutrophils and platelets are essential for host defense and tissue repair, little is known about immune adaptations during their depletion. In this pilot, discovery phase study, we evaluated the plasma proteome of 10 patients with chemotherapy‐induced severe neutropenia and thrombocytopenia, prior to any clinical complication. At sampling, mean neutrophil and platelet counts were 0.15 ± 0.18 × 109/L and 34.6 ± 17.4 × 109/L, respectively. A total of 762 proteins were identified, of which 71 were downregulated and 21 were upregulated in patients compared with healthy controls. Over‐representation analyses revealed that most downregulated proteins were related to immune responses, hemostasis, and protein metabolism. Notably, six upregulated proteins (USP8, IGFBP2, RCN1, B2M, LRG1, and C9) also mapped to these pathways, supporting the hypothesis that they may contribute to early systemic responses to chemotherapy‐induced myelotoxicity and tissue damage. This exploratory study leveraged a unique clinical window to examine how the human immune system responds to the marked reduction of neutrophils and platelets in the context of tissue and barrier disruption. The downregulation profile suggests impairment of the host's immunothrombotic defense, whereas the upregulated proteins may represent early compensatory mechanisms aimed at preserving homeostasis. Together, these findings provide insights into systemic responses during profound cytopenias and highlight candidate proteins that may mediate early adaptations to hematopoietic and tissue injury in patients undergoing intensive chemotherapy.

Background: Eisenmenger syndrome (ES) is a rare complication of congenital heart disease characterized by pulmonary hypertension and bidirectional or reversed shunt. Patients with ES are vulnerable to infections, including dengue virus(DENV), which can further aggravate cardiovascular compromise. Case: A 32-year-old woman with a history of congenital heart disease was admitted with shortness of breath, cyanosis, palpitations, and vomiting. During hospitalization, patientsdeveloped fever, rash, petechiae, and thrombocytopenia. Echocardiography demonstrated an atrial septal defect withbidirectional shunt and pulmonary hypertension, consistent with ES. Laboratory results confirmed dengue hemorrhagic fever (DHF) with hemoconcentration and severe thrombocytopenia. Management included cautious fluid resuscitation,platelet transfusion, corticosteroids, and supportive therapy with sildenafil citrate for pulmonary hypertension. Clinical improvement was achieved, and the patient was discharged after nine days of hospitalization. Conclusion: Thiscase illustrates the complex interaction between ES and DHF, in which increased vascular permeability, coagulation abnormalities, and chronic hypoxemia exacerbate hemodynamic instability. Currently, there are no standardized guidelines for managing dengue in patients with ES; therefore, therapy must be individualized with vigilant monitoring. Recognition of this rare comorbidity is important to prevent complications, optimize treatment, and improve survival.

Acute promyelocytic leukemia (APML) is a rare hematologic emergency with a high mortality rate due to bleeding diathesis, which is due to a disseminated intravascular coagulation-like coagulopathy; APML is complicated enough to treat on its own and becomes particularly challenging when it occurs during pregnancy due to the complexities in managing both maternal and fetal health. APML is associated with a challenging therapeutic dilemma for pregnant women, and there is a risk of fetal malformations and developmental abnormalities caused by exposure to chemotherapy. A 31-year-old woman at 29 weeks of gestation presented with a 3-week history of fatigue. Complete blood count revealed pancytopenia, and further evaluation confirmed a diagnosis of APML. Due to her severe thrombocytopenia and associated pregnancy risks, ATRA therapy was initiated, and a primary Cesarean section was performed at 31 weeks 3 days of gestation to mitigate maternal and fetal complications. After delivery, arsenic trioxide was added to the treatment regimen, resulting in a favorable response. In this case report, we discuss clinical decisions and therapeutic interventions and compare our patient's case with those found in the literature. This case highlights the importance of prenatal care and early intervention in improving outcomes for both mother and child.

Low platelet count is rarely caused by inherited thrombocytopenia. May-Hegglin anomaly is an uncommon condition that falls under the umbrella of familial thrombocytopenia. The condition is under-reported in Saudi Arabia; therefore, we report the current case. This is a 24-year-old Saudi lady, presented to the emergency room with vaginal bleeding. No bleeding occurred at any other sites. She has a positive family history of thrombocytopenia among her father and 2 of her siblings. Her platelet count was 16 × 103/µL with normal other blood count as well as renal and liver panels. She was admitted to the regular bed for investigation as sever thrombocytopenia with suspicion of either familial or immune thrombocytopenia. Further studies showed normal hemostatic, virology, and connective tissue disease markers. Peripheral blood film showed low platelet distribution with occasional large/giant platelets and basophilic inclusion bodies in some neutrophils (Dohle body-like). A picture suggestive of May-Hegglin related thrombocytopenia that was confirmed by the presence of a positive myosin heavy chain 9 (MYH9) gene mutation. In conclusion, there are many difficulties in diagnosing and treating May-Hegglin disorders in females of reproductive age. More research and guidelines are needed to manage inherited thrombocytopenia before and throughout pregnancy.

Comparative Analysis of Lymphodepletion Regimens in CART-19 Treatment for Relapsed/Refractory Diffuse Large B Cell Lymphoma.

We report a case of a patient who developed delayed-onset, persisting autoimmune heparin-induced thrombocytopenia (HIT) following prophylactic anticoagulation with unfractionated heparin (UFH) after surgical treatment of a complex midfacial and mandibular fracture. Four days after stopping prophylactic anticoagulation, the patient developed pulmonary embolism and mild thrombocytopenia. HIT was initially not suspected and therapeutic anticoagulation was started. The patient subsequently developed severe thrombocytopenia consistent with HIT. Despite cessation of UFH and initiation of argatroban, thrombocytopenia did not improve. A HIT-antibody immunoassay and functional assay (HIPA) was strongly positive, and HIPA showed activity even in the absence of heparin, supporting the diagnosis of delayed-onset, persisting autoimmune HIT (aHIT). The patient was treated with immunoglobulin, resulting in a rapid recovery of platelet counts. This case highlights the importance of early recognition and appropriate management of aHIT, especially in patients with persisting thrombocytopenia despite standard HIT therapy.

A rare but fatal illness is drug-induced thrombocytopenia (DITP). Severe thrombocytopenia is not frequently linked to antihistamines, especially first-generation H1 blockers like chlorpheniramine. We describe a rare instance of a 31-year-old man who used chlorpheniramine for rhinitis and thereafter got severe thrombocytopenia (platelet count=0×109/L). The patient had subcutaneous petechiae, bilateral conjunctival hemorrhage, and bleeding gums. Other causes were ruled out by laboratory tests, such as bone marrow analysis and peripheral blood smears. After receiving intravenous immunoglobulin (IVIG) and corticosteroids, the patient's platelet counts gradually recovered. This instance emphasizes how crucial it is to identify DITP as a side effect of chlorpheniramine so that early diagnosis and treatment may be carried out.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 deficiency. Diagnosis is often challenging because most patients do not present with the classic pentad of findings. We report a 56-year-old woman with multiple comorbidities, including systemic lupus erythematosus and antiphospholipid syndrome, who presented with neurologic symptoms, hemolytic anemia, and severe thrombocytopenia without initial schistocytosis. Her condition was initially misattributed to isoniazid-induced thrombocytopenia, resulting in delayed recognition of TTP. Immune-mediated TTP was suspected based on her autoimmune disease history and was definitively confirmed when ADAMTS13 activity returned at <1%. Initiation of plasma exchange, corticosteroids, and caplacizumab led to rapid hematologic recovery. This case underscores the importance of maintaining a high index of suspicion for immune-mediated TTP, particularly in patients with underlying autoimmune disease, as early diagnosis and prompt treatment are critical to preventing fatal thrombotic complications.

MECOM encodes a developmental and haematopoietic transcription factor associated with a rare early-onset syndrome including bone marrow failure, skeletal and other congenital anomalies. Heterozygous de novo variants are the primary cause. We previously identified MECOM as a candidate gene for paediatric pulmonary arterial hypertension (PAH) using trio exome sequencing. To test the role of MECOM in paediatric PAH and further define the clinical phenotype of MECOM-associated syndrome, we queried GeneMatcher and screened rare disease databases for individuals with predicted deleterious MECOM variants. We analysed the clinical spectrum of patients, performed protein modelling of genetic variants and assessed cardiopulmonary expression. We identified 15 individuals with MECOM variants, including 11 unrelated probands and 8 de novo variants. 11 individuals had severe or mild thrombocytopenia, 9 had skeletal issues, 8 had cardiac anomalies, 6 had PAH and 10 had additional conditions. Three were diagnosed in utero and died in the neonatal period. All missense variants map to the zinc finger 6 or zinc finger 8/9 region, a known hotspot for MECOM-associated syndrome. Protein modelling predicted that both regions are DNA-binding, and that the variants may interfere with binding to a VEGFR2/KDR enhancer. Data from LungMAP showed that MECOM is primarily expressed in pulmonary arterial endothelial cells. Rare MECOM variants are associated with early-onset syndromic PAH. PAH monitoring should be considered for all individuals with rare MECOM variants. We speculate that the pathogenetic mechanism for PAH and cardiac defects may be impaired VEGFR2/KDR signalling.

Cholangiocarcinoma (CCA) remains a highly lethal malignancy with a dismal prognosis, primarily driven by therapeutic resistance. A dominant resistance mechanism involves overexpression of anti-apoptotic BCL-2 proteins (BCL-XL, BCL-2, MCL-1). While direct inhibition of these proteins shows efficacy, its clinical utility is frequently limited by dose-dependent hematotoxicity-as exemplified by ABT263, a BCL-XL/BCL-2 dual inhibitor that induces severe thrombocytopenia. We performed integrated analyses of BCL-2 family mRNA/protein expression in clinical CCA specimens and preclinical cell lines. Leveraging proteolysis-targeting chimera (PROTAC) technology, we investigated the therapeutic application of BCL-XL-specific degraders, both as monotherapy and in combination with gemcitabine, to selectively target CCA cells while minimizing hematologic toxicity. Integrated clinical-experimental data identified BCL-XL as a principal determinant of therapeutic sensitivity in CCA. In vitro, the cereblon (CRBN)-based PROTAC XZ739 demonstrated superior efficacy to its von Hippel-Lindau tumor suppressor (VHL)-based counterpart DT2216, reducing CCA cell viability via apoptosis induction. In vivo, XZ739 synergized with gemcitabine to suppress tumor growth in a CCA xenograft model, achieving robust efficacy without significant thrombocytopenia-a critical advance over conventional BCL-XL inhibitors. These findings establish XZ739 as a promising therapeutic candidate for BCL-XL-dependent CCA, highlighting its translational potential for rational combination with chemotherapy to overcome resistance while mitigating hematologic toxicity.

Anti-CD36 isoantibodies can induce platelet transfusion refractoriness and fetal neonatal immune thrombocytopenia. However, the mechanism of platelet clearance mediated by these antibodies (Abs) in such disorders remains unknown.We analyzed platelet clearance caused by mouse and human CD36 monoclonal Abs GZ1 IgG1 and IgG2 subclasses in vitro and in vivo.Platelet clearance was evaluated in vitro by platelet phagocytosis assays and in vivo by monoclonal Ab GZ1 administration to C57BL/6J mice. Platelet activation, apoptosis, and desialylation were analyzed by flow cytometry.Both anti-CD36 Abs subclasses caused lower platelet clearance than anti-αIIbβ3 owing to the FcγR occupancy of monocytes by anti-CD36 Abs. This reaction could lead to mild thrombocytopenia, compared with the severe thrombocytopenia induced by anti-αIIbβ3 platelet-specific Abs. IgG subclass-mediated platelet clearance was inhibited by anti-FcγR Abs and intravenous immunoglobulin (IVIG). The human IgG2 Ab subclass caused lower platelet clearance than IgG1. IgG1- and IgG2-mediated platelet phagocytosis was inhibited by anti-FcγRI and anti-FcγRII, respectively. Unlike IgG1, the IgG2 Ab subclass induced platelet activation, apoptosis, and desialylation and platelet clearance by endothelial cells via Fc-independent pathway.IgG1 and IgG2 subclasses of anti-CD36 Abs triggered platelet clearance primarily via the Fc-dependent pathway. The IgG2 Ab subclass, however, additionally induced platelet clearance via the Fc-independent pathway. These results indicate that the anti-CD36 Ab IgG subclass influences platelet clearance efficiency and may therefore determine the severity of immune thrombocytopenia caused by anti-CD36 antibodies.

ABSTRACTImmune thrombocytopenia (ITP) is a rare but recognized hematologic complication of tuberculosis (TB), particularly miliary TB. We present a case of a 50‐year‐old female with severe thrombocytopenia and hemorrhagic manifestations secondary to miliary TB. The patient presented with mucocutaneous bleeding, anemia, and constitutional symptoms. Investigations revealed severe thrombocytopenia (11,000/μL), erythroid hyperplasia on bone marrow aspiration, and radiographic findings consistent with miliary TB, later confirmed by sputum GeneXpert. Management included short‐course high‐dose dexamethasone for acute bleeding, followed by anti‐tuberculosis therapy (ATT), which led to sustained platelet recovery without further immunosuppression. This case highlights miliary TB as a reversible cause of secondary ITP and underscores the importance of investigating underlying infections in patients presenting with thrombocytopenia in TB‐endemic regions.

Evans syndrome is a rare autoimmune disorder characterized by the simultaneous or sequential occurrence of autoimmune cytopenia. The disease is chronic, relapsing, and frequently refractory to standard therapies. Typical symptoms include anemia-related fatigue, pallor, and jaundice due to hemolysis and petechiae, and purpura and mucosal bleeding due to thrombocytopenia. Treatment often involves a stepwise escalation of immunosuppressive treatments (e.g., corticosteroids, anti-CD20 monoclonal antibodies) and/or stimulants (e.g., thrombopoietin receptor agonists). However, sustained remission remains elusive in many patients. We report the case of a 69-year-old woman with a 19-year history of Evans syndrome, presenting with a life-threatening relapse marked by severe thrombocytopenia and strong hemolytic activity. The patient had previously undergone multiple treatment regimens and had developed comorbidities that both complicated disease management and treatment strategies. Despite repeated therapeutic interventions with various immunosuppressant agents, she remained transfusion-dependent and clinically unstable and experienced various treatment complications. Additionally, targeting antibody-producing plasma cells with daratumumab (anti-CD38) led to a rapid fall in transfusion dependency, clinical stabilization, and transition to outpatient care. Unfortunately, the patient later succumbed to infectious complications after a femoral fracture. This case underscores the therapeutic complexity of multirefractory Evans syndrome and the limitations of conventional therapy. The addition of daratumumab, resulting in depletion of CD38 + plasma cells, helped achieve hematologic stabilization in this refractory case.

Kasabach-Merritt phenomenon (KMP) is a rare condition associated with vascular tumors such as kaposiform hemangioendothelioma and tufted angioma; it can be life-threatening due to its consumptive coagulopathy. Thrombocytopenia and hypofibrinogenemia are characteristic of KMP, and anemia and raised d-dimer levels can also be detected. Here, we report a 7-month-old Cambodian with the condition. The infant was admitted to the National Pediatric Hospital in Phnom Penh because of a mass on the right side of the neck that had been progressively enlarging. The patient had severe thrombocytopenia (8,000/µL), anemia (Hb 7.6g/dL) and reduced fibrinogen level (1.5g/L). CT scan suggested and histopathology of the lesion confirmed a diagnosis of kaposiform hemangioendothelioma. Kasabach-Merritt phenomenon was diagnosed, and the infant was treated with platelets and fresh frozen plasma infusions, prednisolone (2mg/kg/day) and propranolol (2.5mg/kg/day). After eight weeks of therapy, platelets raised to 102,000/µL. The infant developed Cushing’s syndrome after 6 months of treatment, and prednisolone was scaled down to a maintenance dose of 0.5mg/kg/day. Fibrinogen levels went back to normal (2.14g/L) after seventeen months of treatment, and the tumor shrunk significantly. This case report shows that a combination of prednisolone and propranolol was effective for the treatment of KMP and kaposiform hemangioendothelioma. Timely recognition and treatment of Kasabach-Merritt phenomenon is essential.