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Thrombocytopenia has been identified as a common complication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the general population. In an attempt to determine the impact of coronavirus disease 2019 (COVID-19) in patients with immune thrombocytopenia (ITP), a retrospective single-centre study was performed. Thrombocytosis was observed in patients with chronic ITP after SARS-CoV-2 infection, frequently needing treatment adjustment or even discontinuation of therapy. Relapses and newly diagnosed cases showed a fast response after initial treatment compared to ITP. Reduced immune activity due to lymphopenia during COVID-19 could explain this paradoxical effect, although further studies are needed., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Coronavirus disease 2019 (COVID-19) can affect the haematopoietic system. Thrombocytopenia at admission was prevalent, while late-phase or delayed-phase thrombocytopenia (occurred 14 days after symptom onset) is rare. This retrospective, single-centre study screened 450 COVID-19 patients and enrolled 271 patients at the Union Hospital, Wuhan, China, from January 25 to March 9, 2020. COVID-19-associated delayed-phase thrombocytopenia occurred in 11·8% of enrolling patients. The delayed-phase thrombocytopenia in COVID-19 is prone to develop in elderly patients or patients with low lymphocyte count on admission. The delayed-phase thrombocytopenia is significantly associated with increased length of hospital stay and higher mortality rate. Delayed-phase nadir platelet counts demonstrated a significantly negative correlation with B cell percentages. We also provided and described bone marrow aspiration pathology of three patients with delayed-phase thrombocytopenia, showing impaired maturation of megakaryocytes. We speculated that immune-mediated platelet destruction might account for the delayed-phase thrombocytopenia in a group of patients. In addition, clinicians need to pay attention to the delayed-phase thrombocytopenia especially at 3-4 weeks after symptom onset., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

A case of severe fever with thrombocytopenia syndrome (SFTS) in which a skin biopsy from the tick-bite region was analyzed is reported. The patient was a 72-year-old woman who developed fever and thrombocytopenia after a tick bite. SFTS was diagnosed from polymerase chain reaction (PCR) analysis of a blood sample. Histopathological analysis of a skin biopsy specimen from the tick-bite region showed CD20-positive perivascular and interstitial immunoblastic cells, which were positive to anti-SFTS virus (SFTSV) nucleoprotein antibody. In addition, SFTSV RNA was detected by real-time PCR from this biopsy specimen. Moreover, hemophagocytosis was also found in the tick-bite region. To the best of our knowledge, this is the first report to analyze the details of the tick-bite region of skin in SFTS, and the first to detect virus-infected cells in the skin. The present findings may help elucidate the mechanisms of entry of SFTSV., (© 2019 Japanese Dermatological Association.)

Infections continue to cause a high incidence of mortality and morbidity in resource-poor nations. Although antimicrobial therapy has aided mostly in dealing with the pathogenic micro-organisms themselves, the collateral damage caused by the infections continue to cause many deaths. Intensive care support and manipulation of the hosts' abnormal response to the infection have helped to improve mortality in well-resourced countries. But, in those areas with limited resources, this is not yet the case and simpler methods of diagnosis and interventions are required. Thrombocytopenia is one of the most common manifestations in all these infections and may be used as an easily available prognostic indicator and marker for the severity of the infections. In this review, the relevance of platelets in infections in general, and specifically to tropical infections, malaria, and viral haemorrhagic fevers in the emerging countries is discussed. Better understanding of the pathophysiology and the role of platelets in particular in such conditions is likely to translate into better patient care and thus reduce morbidity and mortality., (© 2017 John Wiley & Sons Ltd.)

Hepatitis E virus can cause acute, fulminant and chronic hepatitis and has been associated with a range of extrahepatic manifestations. Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis are the main neurological manifestations associated with acute and chronic hepatitis E virus infection. Renal injuries have been also reported, including membranoproliferative glomerulonephritis with or without cryoglobulinemia and membranous glomerulonephritis. Acute pancreatitis, haematological disorders and other autoimmune extrahepatic manifestations of hepatitis E virus, such as myocarditis and thyroiditis, have been also reported. In this comprehensive article, we review all published reports describing hepatitis E virus-associated extrahepatic manifestations., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To examine (1) the incidence of fetal thrombocytopenia in hydropic fetuses with congenital B19 virus infection, (2) the effect of intrauterine platelet transfusions and (3) the correlation between fetal B19 viral load and severity of thrombocytopenia., Design: Retrospective analysis of data from prospectively collected fetal blood samples., Setting: Leiden University Medical Centre, the national centre for management of intrauterine fetal disease in the Netherlands., Population: Thirty hydropic fetuses treated with intrauterine red blood cell and platelet transfusions for human B19 virus-induced severe fetal anaemia and thrombocytopenia over a 10-year period., Methods: Fetal blood samples (n= 30) taken before and after intrauterine transfusion were investigated. No cases were excluded, and there was no loss to follow up., Main Outcome Measures: Parameters recorded were gestational age, experienced fetal movements, gravidity and parity, severity of fetal hydrops, severity of fetal anaemia and thrombocytopenia and megakaryocyte and reticulocyte counts. Survival and procedure-associated complications were documented. Quantitative B19 viral load measurements were performed on all fetal samples., Results: Forty-six percent of all hydropic fetuses showed severe thrombocytopenia. No antenatal intracerebral haemorrhage or procedure-associated bleeding occurred. Overall, survival was 77%. Platelet counts increased following platelet transfusion and decreased significantly following red blood cell transfusion alone. No correlation was found between fetal viral loads and platelet counts., Conclusion: Thrombocytopenia was frequently encountered in fetal B19V infection, but fetal bleeding complications were not noted. Absence of a direct relationship between fetal B19 viral load and platelet counts suggests a temporal dissociation between these findings. Dilutional thrombocytopenia is frequently seen in the fetus following red blood cell transfusion alone. The clinical significance of this phenomenon is unclear. The risk of fluid overload by fetal platelet transfusion in a severely hydropic fetus should be weighed against the low incidence of fetal bleeding complications.

Thrombocytopenia can be a complication of hepatitis C viral (HCV) infection. However, there is little published data regarding the clinical and laboratory manifestations of HCV-related thrombocytopenia (HCV-TP) compared with adult chronic immune thrombocytopenic purpura (CITP). We reviewed the medical records for all patients evaluated for chronic thrombocytopenia by the Haematology Service between January 1996 and June 2000. All patients were screened for HCV infection at the time of initial diagnosis. Of 250 patients who fulfilled American Society of Hematology criteria for CITP, 76 (30%) were HCV seropositive. HCV-TP patients were older [mean age (+/-SD) 54.9 +/- 8 years vs. 40.3 +/- 8 years, P

A replication-incompetent adenovirus vector was administered to rhesus macaques at 1, 3 and 6 x 1012 particles/kg doses to investigate its toxicity. Platelet count decrements of 28%, 82% and 90%, respectively, were observed, with corresponding platelet half-lives of 69.0, 25.2 and 22.2 h (compared with 111 h in untreated animals). The platelet decline was equivalent for all three doses for 8 h, and platelet count recovery began as early as 8 h after infusion for low-dose recipients, or as late as 24 h for the medium and high dose recipients. These observations suggest that thrombocytopenia is a saturable, reversible consumptive process.

Thrombocytopenia is a common extrahepatic manifestation of hepatitis C (HCV) infection. Treatment with steroids may be effective, but can exacerbate the viral infection. Interferon alpha (INF) has documented efficacy in the treatment of HCV, but its use in the treatment of HCV thrombocytopenia is controversial. We treated eight patients with HCV-related thrombocytopenia, who had platelet counts of fewer than 50 x 10(9)/l (range: 16 to 46 x 10(9)/L) with INF 3 MU SQ three times a week. Planned duration of treatment was 24 weeks. Five patients had no evidence of hepatic cirrhosis, three had cirrhosis, and two had palpable splenomegaly. Only three patients tolerated the full course of treatment, and all three had improvement in their platelet counts to greater than 50 x 10(9)/l. Two other patients had improvement in platelet counts to more than 50 x 10(9)/l with shorter duration of treatment (six and 16 weeks, respectively). The mean increase in platelet count in the five responders was 44 x 10(9)/lL (range: 28 to 90 x 10(9)/l). The average peak platelet count in the responders was 81 x 10(9)/l (range: 62 to 136 x 10(9)/l). Duration of response ranged from four to 18+ months, with the shortest responses observed in the two patients treated with a shorter course of INF. Response was independent of the presence of cirrhosis. Responding patients had improvement in hepatic transaminases, reduction in cryoglobulin and anticardiolipin antibodies, and HCV plasma RNA when tested. Relapse was associated with an increase in these laboratory markers of HCV infection. We conclude that INF can be an effective treatment in patients with HCV-related thrombocytopenia., (Copyright 2001 Wiley-Liss, Inc.)

Hepatitis C virus (HCV) has been proposed as a possible causative agent of chronic thrombocytopenia. We investigated HCV infection in a series of 51 unselected Spanish patients with chronic acquired thrombocytopenia. Anti-HCV and HCV viraemia were detected in 13/51 (22.5%) of cases; this prevalence was particularly significant when compared with HCV seropositivity in age-matched controls (0.4%). Anti-HCV-positive patients, four men and nine women with a median age of 59.3 years (range 36-72), had a mean platelet count of 55.8 x 109/l (range 12-96). Only one of our HCV-positive thrombocytopenic patients had hypersplenism. Platelet-associated IgG (PAIgG) was negative, as measured by immunofluorescent flow cytometric analysis in 11/13 HCV-positive thrombocytopenic patients. Thus, thrombocytopenia in our HCV-positive patients appeared to be non-autoimmune mediated. In six patients, a trial of recombinant alpha2b-interferon (IFN-alpha) given at a dose of 3 MU three times per week for 6-24 months gave a durable (> 1 year) and significant increase in platelet count in all six patients. The maximum increase occurred after 6 months of IFN-alpha therapy. In conclusion, the ability of IFN-alpha to increase platelet counts in HCV-positive thrombocytopenic patients supports mechanisms involving a direct role for HCV inhibiting platelet production.

Thirteen cases of fetal parvovirus B19 infection with hydrops foetalis are reported. Viral DNA was identified by polymerase chain reaction (PCR) of amniotic fluid sampled between the 19th and the 29th week of gestation. Haematological examination revealed severe anaemia in all cases and thrombocytopenia in 11/13 cases, which was severe in two cases. Six fetuses died in utero; two after intrauterine transfusion. Complete recovery was observed in seven fetuses; five cases were treated by intrauterine transfusions, and in two cases spontaneous recovery occurred. Upon follow-up, no case of congenital anaemia was observed.

The levels of platelet-associated Igs (PAIgs) and plasma circulating antiplatelet antibodies were evaluated by a flow cytometric immunofluorescence assay (FCIFA), an enzyme-linked immunoassay (ELISA), and a platelet radioactive antiglobulin test (PRAT), in a group of 45 human immunodeficiency virus (HIV)-infected intravenous drug users (IVDUs), with or without thrombocytopenia (TCP). Direct tests demonstrated an increased amount of PAIgs in 40% of the patients, irrespective of their platelet count. These PAIgs were mainly of IgG class and could not be eluted with ether. Plasma IgG with antiplatelet activity was found in 70% of the thrombocytopenic individuals, whereas it was detected in only one patient without TCP. The relative frequencies of antibodies against the platelet glycoproteins (GPs) Ib/IX and IIb/IIIa were assessed in plasma from all patients by means of the monoclonal antibody-specific immobilization of platelet antigens assay (MAIPA). Plasmas from all non-thrombocytopenic patients were negative when tested by indirect MAIPA. In contrast, 10/23 plasma from thrombocytopenic patients reacted with either GP IIb/IIIa, GP Ib/IX, or both GPs. Finally, aiming to investigate whether HIV antibodies from these patients are reactive with normal platelets, we performed absorption-elution experiments, followed by evaluation of HIV antibodies in the indirect eluates by ELISA and Western blot. Interestingly, we detected anti-HIV antibodies that bind to normal platelet antigens in 50% of the ether eluates prepared from control platelets sensitized with plasma from patients with TCP, but in only 5% of eluates obtained from platelets sensitized with plasma from non-thrombocytopenic patients. The present study provides direct evidence that specific autoantibodies against platelet membrane GPs Ib/IX and IIb/IIIa are common in HIV positive thrombocytopenic individuals. The finding in these patients of HIV antibodies cross-reactive with normal platelets, suggests that mimicry of human antigens by HIV could play a key role in the pathophysiology of the HIV-related TCP.

Glycoproteic (GP) IIb/IIIa+ megakaryocytic cells were purified from the bone marrow (BM) of 15 HIV-1 seropositive thrombocytopenic patients, eight HIV-1 seronegative patients affected by immune thrombocytopenic purpura (ITP) and 14 HIV-1 seronegative normal donors. The presence of apoptosis was evaluated in freshly isolated GPIIb/IIIa+ cells by flow cytometry after propidium iodide staining and electron microscopy. GPIIb/IIIa+ cells from HIV-1 seropositive thrombocytopenic patients showed a significant (P < 0.0001) increase of apoptosis with respect to both HIV-1 seronegative ITP patients and normal donors. Moreover, the degree of apoptosis in bone marrow GPIIb/IIIa+ cells purified from HIV-1 seropositive thrombocytopenic patients was inversely (P < 0.01) related to the count of circulating platelets, whereas it did not show any significant correlation with the absolute number of circulating CD4 T cells, the CD4/CD8 ratio or the presence of proviral gag DNA sequences. Therefore neither an advanced stage of HIV-1 disease nor a direct infection with HIV-1 seems to play a primary role in the impaired survival of BMGPIIb/IIIa+ megakaryocytic cells. These findings strengthen the notation that, besides the immune targeting of peripheral platelets, an impairment of the bone marrow megakaryocyte compartment may also contribute to the pathogenesis of HIV-1 related thrombocytopenia.

We describe a patient with severe symptomatic thrombocytopenia and haemolytic anaemia caused by cytomegalovirus (CMV) infection. As far as we know, this is the second case in the literature. Treatment with ganciclovir seemed to be more effective for thrombocytopenia than treatment with corticosteroids. The hypothetical mechanisms leading to thrombocytopenia and haemolysis in CMV infection are briefly discussed. In cases of acute thrombocytopenia and clinical manifestations of an infectious disease, with or without haemolysis, testing for CMV may be useful in connection with therapeutic consequences.

The Epstein-Barr virus (EBV), or human herpesvirus-6 (HHV-6) associated haemophagocytic lymphohistiocytosis, has been found prevalent in Taiwan; it affects previously healthy children and is always fatal when treated only supportively. Recognition of the underlying pathogenesis for this disease prompted adoption of an immunomodulatory regimen of intravenous immunoglobulin (IVIG) and/or etoposide on 17 such patients treated between 1990 and 1993. Remarkable improvement in patients' prognoses was demonstrated. Eight patients are still alive with a median follow-up of 1 year and 2 months post-treatment. Both IVIG and etoposide had positive immunomodulation effects such as alleviation of fever and normalization of haematological and hepatic parameters. Sustained complete response was obtained in two of nine cases of EBV-associated diseases treated with IVIG only. EBV transcripts became undetectable after etoposide and/or IVIG treatment without antiviral agents. Etoposide given by split-doses schedule appeared to be superior to conventional three-consecutive-days schedule for both remission induction and disease-free survival. Our preliminary trial apparently provides a promising improvement in the treatment of this previously fatal disease. IVIG or etoposide is effective in reversing the process of lymphohistiocytic dysregulation resulting from virus infection of immune cells in this syndrome and probably helps hosts to control active virus replication in certain cases, through immunomodulation.