A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumor s and hematologic malignancies

Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy treatment delays, dose reductions, and discontinuation. There is no US Food and Drug Administration (FDA)-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at four US centers. The primary outcome was achievement of a romiplostim response (median on-romiplostim platelet count ≥75x10⁹/L and ≥30x10⁹/L above baseline). Secondary outcomes included time to platelet count ≥100x10⁹/L and rates of the following: platelet count <100×10⁹/L, platelet count <75x10⁹/L, platelet count <50x10⁹/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. A total of 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of four (range: 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays, and 89% avoided platelet transfusions. Median per-patient platelet count on romiplostim was significantly higher than baseline (116x10⁹/L vs. 60x10⁹/L; P<0.001). Bone marrow (BM) tumor invasion, prior pelvic irradiation, and prior temozolomide exposure predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays/bleeding; intracycle dosing had an incidence rate ratio (IRR) for dose reduction/treatment delay of 3.00 (95%CI: 1.30-6.91; P=0.010) and an IRR for bleeding of 4.84 (95%CI: 1.18-19.89, P=0.029) compared with weekly dosing. Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with BM involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.     

A randomized placebo-controlled trial of recombinant human interleukin- 11 in cancer patients with severe thrombocytopenia due to chemotherapy

Thrombocytopenia is a complication of cancer treatment that can limit dose intensity. Interleukin-11 (IL-11) is a growth factor that increases platelet production. We conducted a multicenter, randomized, placebo-controlled trial of recombinant human IL-11 (rhIL-11) in 93 patients with cancer who had already been transfused platelets for severe thrombocytopenia resulting from chemotherapy. The patients had received platelet transfusions for nadir platelet counts of < or = 20,000/microL during the chemotherapy cycle immediately preceding study entry. Chemotherapy was continued during the study without dose reduction. Patients were randomized to receive placebo or rhIL-11 at 50 or 25 micrograms/kg subcutaneously once daily for 14 to 21 days beginning 1 day after chemotherapy. Eight of 27 (30%) evaluable patients treated with rhIL-11 at a dose of 50 micrograms/kg did not require platelet transfusions versus 1 of 27 (4%) patients who received placebo (P < .05). Five of 23 (18%) patients treated with rhIL-11 at 25 micrograms/kg avoided platelet transfusions (P = .23). Side effects were fatigue and cardiovascular symptoms, including a low incidence of atrial arrhythmias and syncope. There were no differences among treatment groups in the incidence of neutropenic fever, days of hospitalization, or number of red blood cell transfusions. This study shows that rhIL-11 treatment of a dose of 50 micrograms/kg significantly increases the likelihood that patients who have already been transfused platelets for severe chemotherapy-induced thrombocytopenia will not require platelet transfusions during a subsequent chemotherapy cycle.     

Recombinant human thrombopoietin attenuates carboplatin-induced severe thrombocytopenia and the need for platelet transfusions in patients with gynecologic cancer

BACKGROUND: Thrombocytopenia is a significant problem in the treatment of cancer. OBJECTIVE: To assess the clinical safety of therapy with recombinant human thrombopoietin (rhTPO) and its ability to ameliorate chemotherapy-induced severe thrombocytopenia. DESIGN: Phase I/II clinical cohort study. SETTING: The University of Texas M.D. Anderson Cancer Center, Houston, Texas. PATIENTS: 29 patients with gynecologic cancer. INTERVENTION: Recombinant human thrombopoietin was given before chemotherapy and after a second cycle of carboplatin therapy. MEASUREMENTS: Peripheral blood counts and platelet transfusions. RESULTS: Administration of rhTPO after chemotherapy significantly reduced the degree and duration of thrombocytopenia and enhanced platelet recovery. In patients who received the optimal biological dose of rhTPO (1.2 microg/kg of body weight) in cycle 2 (carboplatin plus rhTPO), the mean platelet count nadir was higher (44x10(9) cells/L and 20x10(9) cells/L; P = 0.002) and the duration of thrombocytopenia was shorter (days with a platelet count <20x10(9) cells/L, 1 and 4 [P = 0.002]; days with a platelet count <50x10(9) cells/L, 4 and 7 [P = 0.006]) than in cycle 1 (carboplatin only). The need for platelet transfusion in this group was reduced from 75% of patients in cycle 1 to 25% of patients in cycle 2 (P = 0.013). CONCLUSIONS: Therapy with rhTPO seems to be safe and may attenuate chemotherapy-induced severe thrombocytopenia and reduce the need for platelet transfusions.     

Acute bleeding complications in patients after bone marrow transplantation

Acute bleeding is a frequent complication that commonly associates with increased morbidity after bone marrow transplantation. Except for diffuse alveolar hemorrhage and cerebral hemorrhage, bleeding is infrequently recorded as a direct cause of death. Yet outcome analyses showed that bleeding from any reviewed site was associated with reduced survival. Reduced survival was correlated with bleeding intensity and the number of bleeding sites. These data point to the need to monitor all manifestations of bleeding, as bleeding may identify patients at risk for bone marrow transplantation toxicity. Until recently, prophylactic platelet transfusions were commonly given at a trigger of 20 x 10(9)/L. Whereas bleeding is more likely to occur when platelet counts drop to low levels, most bleeding episodes were recorded with platelet counts greater than 20 x 10(9)/L, suggesting causes other than profound thrombocytopenia in the pathogenesis of bleeding. Given that a trigger of 10 x 10(9)/L has become accepted for prophylactic platelet transfusions, care should be taken to ensure that parameters other than the incidence of bleeding have not been adversely affected.     

Phytochemicals as potential therapeutics for thrombocytopenia

Medical knowledge has always relied on plants as the main sources of important beneficial compounds. Many species have been recognized to have medicinal properties and beneficial impact on health, e.g. antioxidant activity, digestive stimulation action, anti-inflammatory, antimicrobial, hypolipidemic, antimutagenic and anticarcinogenic potential. This review focuses on the promising role of plants and their products in attenuating thrombocytopenia, a common and complex bleeding disorder. When the platelet count decreases below 150,000/µl, it causes thrombocytopenia. This bleeding disorder is observed in 2.5 % of the normal population. The risk of spontaneous muco-cutaneous bleeding and life threatening intracranial haemorrhage or gastrointestinal bleeding increases rapidly when the platelet count decreases below 10,000/µl. The inability to provide supportive treatment to increase the platelet counts often proves fatal to patients. Currently, treatment for thrombocytopenia includes use of drugs or splenectomy or platelet transfusions, in severe cases. Recently, studies have shown platelet augmenting activity of various plant extracts. The effectiveness, toxicity and side effects of the phytochemicals have to be critically evaluated in clinical trials. An in depth understanding of the role and mechanism of these phytochemicals would lead to their successful implementation in treatment and management of thrombocytopenia and other related bleeding disorders.     

Bleeding due to thrombocytopenia in acute leukemias and reevaluation of the prophylactic platelet transfusion policy

Prophylactic platelet administration is indicated at counts below 20 X 10(9)/l. The bleeding tendency and severity were compared between thrombocytopenic patients with acute-lymphocytic leukemia (ALL) and acute non-lymphocytic leukemia (ANLL) in the ranges of 10-20 X 10(9)/l platelets, while prophylactic platelet administration was given only below 10 X 10(9)/l. The bleeding tendency for ALL was quite similar at platelet counts above or below 10 X 10(9)/l. The bleeding tendency was significantly lower (p less than 0.001) when the platelets were above this level in ANLL patients. When the thrombocytopenia was caused by chemotherapy, the bleeding was significantly lower in both types of leukemia above 10 X 10(9)/l (p less than 0.05 for ALL, p less than 0.001 for ANLL) as compared with lower counts. When the thrombocytopenia was caused by leukemia, the bleeding tendency was similar in both types of leukemia and at all platelet counts (below 20 X 10(9)/l). Fever, not associated with sepsis, augmented the bleeding severity of patients with ANLL. Stable or rising counts of platelets were associated with significantly lower bleeding tendency above 10 X 10(9)/l only in ANLL patients. The decision for prophylactic platelet administration at counts below 20 X 10(9)/l should be guided by the type of the leukemia (ALL vs. ANLL), the cause of thrombocytopenia (chemotherapy vs. leukemia per se), the trend of the platelet counts, presence of fever and patient's age (below or above 18 years).(ABSTRACT TRUNCATED AT 250 WORDS)     

Platelet apoptosis in paediatric immune thrombocytopenia is ameliorated by intravenous immunoglobulin

To evaluate the role of intravenous immunoglobulin (IVIg) in platelet apoptosis in paediatric immune thrombocytopenia, we investigated the platelets of 20 paediatric patients with acute immune thrombocytopenia (ITP), before and after IVIg treatment. Healthy children with platelet counts in the normal range and children with thrombocytopenia due to chemotherapy were enrolled as controls. All ITP patients presented with platelet counts <20 × 10⁹/l and bleeding symptoms. Markers of apoptosis, including activated caspase‐3, ‐8 and ‐9, phosphatidylserine (PS) exposure, mitochondrial inner membrane potential (ΔΨm), as well as platelet‐derived microparticle formation, were analysed by flow cytometry. After IVIg treatment, platelet counts increased to >20 × 10⁹/l in all patients. ITP patients had significantly increased proportions of platelets with activated caspase‐3, ‐8 and ‐9, with PS exposure, and with decreased ΔΨm, and demonstrated increased microparticle formation. Except for ΔΨm, these markers for apoptosis were reduced by IVIg treatment. Platelets of children with thrombocytopenia after chemotherapy also demonstrated increased microparticle formation and decreased ΔΨm, but no activation of caspases 3, 8 and 9 or PS exposure. In conclusion, in acute paediatric ITP, enhanced platelet apoptosis is seen at diagnosis that normalizes after IVIg treatment.     

Heparin-induced thrombocytopenia: A prospective study

Thrombocytopenia is a well-described complication of heparin therapy. Few studies describe the incidence of thrombocytopenia when low-dose heparin (10,000–15,000 units/day) is used for prophylaxis of deep venous thrombosis. In our study, ten of 66 courses (15%) of heparin prophylaxis in coronary care unit patients were accompanied by a mild thrombocytopenia with platelet counts below 150 ± 10³/mm³. In all cases the platelet count returned to normal despite continued heparin therapy. Patients who became thrombocytopenic had significantly lower initial platelet counts. No cases of severe thrombocytopenia were seen (platelet count below 100 ± 10³/mm³). No patient developed thrombosis, bleeding or elevated fibrin split products. Mild thrombocytopenia occuring after 2–5 days of low-dose heparin is common, but clinically insignificant.     

Preprocedural prophylaxis with blood products in patients with cirrhosis: Results from a survey of the Italian Association for the Study of the Liver (AISF)

IntroductionThe concept of rebalanced hemostasis in cirrhosis challenges the policy of transfusing plasma or platelets before invasive procedures in patients with prolonged PT or severe thrombocytopenia. Recent guidelines recommend against plasma transfusion and suggest avoiding/minimizing platelet transfusions.AimWe assessed how hepato-gastroenterologists manage prolonged PT/INR or severe thrombocytopenia before invasive procedures.MethodsOn May 2021, AISF members were sent a questionnaire addressing the PT/INR and platelet thresholds required before invasive procedures, the use of other markers of bleeding risk or other hemostatic treatments and the burden of pre-emptive plasma and platelet transfusions.ResultsOf 62 respondents, 94% and 100% use PT/INR and platelet count to assess bleeding risk, respectively. Only 37% and 32% require less conservative PT/INR or platelet counts thresholds for low-risk procedures, respectively. As for those applying single thresholds, 68% require PT/INR <1,5 and 86% require platelet counts ≥50 × 10⁹/L. Half respondents use additional indicators of bleeding risk and 63% other hemostatic treatments. Low-risk procedures account for 70% of procedures, and for 50% and 59% of plasma and platelets units transfused, respectively.Conclusionsthe survey indicates lack of compliance with guidelines that advise against plasma and platelet transfusions before invasive procedures and the need for prospective studies and inter-society consensus workshops.     

Acute bleeding and thrombocytopenia after bone marrow transplantation

The relationship between hemorrhage and low platelet count was first established in patients with acute leukemia, and has been widely applied to thrombocytopenic patients, including BMT patients. Yet, the role of thrombocytopenia in bleeding post BMT has not been systematically studied. We evaluated the risk of bleeding and outcome associated with thrombocytopenia in BMT patients who had prophylactic platelet transfusions at a trigger of 20 x 10(9)/l. Thrombocytopenia was investigated in 321 patients with moderate or severe bleeding (BLD), and in a matched comparison group of 287 patients who did not bleed (NBLD). Profound thrombocytopenia (< or = 10 x 10(9)/l) was found in 8.6% of the BLD patients during the week before the bleeding onset, significantly more frequent than in NBLD patients (2.1% to 4%, P < 0.02), during weeks 2 to 6 post BMT (the period when 75% of the bleeding initiated). On the first day of bleeding, platelet counts < or = 10 x 10(9)/l were found in 13.5%, 11-20 x 10(9)/l in 20.4%, and > 20 x 10(9)/l in 66.1% of all episodes. Overall survival in BLD patients was not associated with the severity of thrombocytopenia before bleeding onset. Severity of thrombocytopenia was significantly associated with reduced survival in NBLD patients. We concluded that bleeding post BMT was significantly associated with thrombocytopenia, but the attributable risk of bleeding from profound thrombocytopenia was not large. Thrombocytopenia may be an important clinical sign in NBLD patients, and should be further explored in relation to acute toxicities other than bleeding.     

Thrombocytopenia and bleeding in dental procedures of patients with Gaucher disease

Summary. The risk of bleeding during dental procedures may be increased in patients with Gaucher disease. We aimed to evaluate potential coagulation and platelet function abnormalities and targeted therapy accordingly. Patients with type 1 Gaucher disease who were treated at the Oral and Maxilo‐Facial surgery clinic at Sheba Medical Center between 2003 and 2010 comprised the study cohort. Data collected included disease history, enzyme treatment, platelet counts, dental therapy and outcome. Bleeding was defined as excessive bleeding during or immediately following procedure. Coagulation studies and platelet function tests including aggregometry were performed on all patients. Dental procedures (n = 14, including eight teeth extractions, two crown lengthening procedures, one cyst enucleation and three deep dental scaling) of seven patients were studied. Mean platelet count prior to procedure was 73 K ± 14.8 mm³. Patients bleeding risk score was calculated according to previous history of bleeding tendency, degree of thrombocytopenia, presence of comorbid coagulopathy and the type of dental procedure. Two patients with highest risk score received prophylactic platelet transfusions, three patients (medium‐risk) received DDAVP preprocedure and all received systemic tranexamic acid, which was the only systemic therapy for low‐risk patients. Meticulous surgical local haemostasis was applied. No excessive intra‐operative or postoperative bleeding occurred. Patients with Gaucher disease who have thrombocytopenia and abnormal platelet function tests may be safely treated if meticulous haemostasis is applied along with systemic therapy as required. Platelet transfusions are not mandatory and should be applied considering the procedure‐related risk and the patient’s calculated haematological risk for bleeding.     

Tranexamic acid therapy in acute myeloid leukemia: possible reduction of platelet transfusions

We studied the clinical efficacy and safety of the antifibrinolytic drug tranexamic acid (TA) in patients undergoing chemotherapy for acute leukemia. 54 newley diagnosed AML patients were treated with 1 g of TA every 6 hours until the platelet count rose to above 20 x 10(9)/l. Platelet transfusions were given, irrespective of the count, only when oral, mucosal or significant skin bleeding manifestations were observed. During induction, the average number of days with thrombocytopenia below 20 x 10(9)/l was 14.4 +/- 7.4 and 4.6 +/- 4.1 transfusions were given in each course. During consolidation, the average number of thrombocytopenic days was 8.4 +/- 8.5 and only 1.7 +/- 1.8 transfusions were administered. In 11.5% of the induction and 32.1% of the consolidation courses, no platelet support was required. TA was tolerated very well and no side effects or thromboembolic complications were observed. Only in 6 of the 78 induction courses did a major bleeding event occur and there were none in any of the 53 consolidation courses. Thus it seems that TA therapy allowed a significant reduction in the use of platelet transfusions without submitting the patients to greater bleeding risks.     

Risk of bleeding and use of platelet transfusions in patients with hematologic malignancies: recurrent event analysis

A recent randomized trial (TOPPS) compared prophylactic platelet transfusions (for counts <10×10⁹/L) with a strategy of no-prophylaxis in adults with hematologic malignancies. Seventy percent of enrolled patients received an autologous hematopoietic stem cell transplant. Statistical models were developed to explore which patient factors or clinical characteristics are important prognostic factors for bleeding. These models were presented for baseline characteristics and for recurrent analysis of bleeding to assess the risks of World Health Organization grade 2–4 bleeding on any given day. Additional analyses explored the importance of fever. Treatment plan (chemotherapy/allogeneic hematopoietic stem cell transplant), female sex, and treatment arm (no-prophylaxis) were significantly associated with an increased number of days of bleeding. The number of days with a platelet count <10×109/L was significantly associated with a grade 2–4 bleed (P<0.0001). Patients with a temperature of at least 38°C had the highest hazard of a grade 2–4 bleed (hazard ratio: 1.7, 95% confidence interval: 1.3 to 2.4, compared with the risk in patients with a temperature <37.5°C). There was no evidence that minor bleeding predicted a grade 2–4 bleed. The results highlighted the limited role of correction of thrombocytopenia by platelet transfusion in reducing the risk of bleeding. Clinically stable patients undergoing autologous hematopoietic stem cell transplantation had the lowest risk of bleeding and benefited least from prophylactic platelet transfusions. Prospective studies are required to address the usefulness of risk factors to support better targeted platelet transfusions. TOPPS Controlled-Trials.com number ISRCTN08758735.     

European collaborative study of the antenatal management of feto-maternal alloimmune thrombocytopenia

The aims of this study were to determine whether the severity of fetomaternal alloimmune thrombocytopenia (FMAIT) in the current pregnancy could be predicted from the history of FMAIT in previous pregnancies, and to assess the effects of different types of antenatal intervention. Fifty-six fetuses were studied that all had a sibling affected by FMAIT due to human platelet antigen 1a (HPA-1a) alloimmunization. Cases with a sibling history of antenatal intracranial haemorrhage (ICH) or severe thrombocytopenia (platelet counts of < 20 x 109/l) had significantly lower pretreatment platelet counts than cases whose siblings had less severe thrombocytopenia or postnatal ICH. Maternal therapy resulted in a platelet count exceeding 50 x 109/l in 67% of cases. None of the fetuses managed by serial platelet intrauterine transfusions (IUT) suffered ICH following treatment. However, several serious complications arose with fetal blood sampling (FBS). Overall, intervention improved outcome, as three study cases suffered from antenatal ICH and three others died whereas 15 study cases had a sibling with an ICH, eight of whom died. The results of this study suggest that the start of therapy can be stratified on the basis of the sibling history of FMAIT, and support the use of maternal therapy as first-line treatment.     

An audit of the use of platelet concentrates in the prophylaxis of thrombocytopenic haemorrhage in a large haematology unit.

Platelet transfusions are valuable in the prevention of thrombocytopenic bleeding in patients undergoing chemotherapy for haematological malignancies. The commonly used threshold platelet count for transfusion of 20 x 10(9)/l was established in the 1960s when the clinical situation was very different from today. Review of the use of platelet concentrates in a large haematology unit showed lack of adherence to this threshold with the use of platelet transfusions at higher platelet counts. Major bleeding episodes occurred at counts above the threshold when additional clinical factors were operating. A lower threshold was therefore recommended and instituted. This resulted in a 20% reduction in the use of platelet concentrates with no increase in major bleeding episodes.     

Feasibility and usefulness of self-assessment of bleeding in patients with haematological malignancies, and the association between platelet count and bleeding

Background and Objectives The aim of this study was to evaluate the collection of daily prospective information about bleeding outcomes in patients with thrombocytopenia, including information obtained by patient self‐assessment. Materials and Methods Consecutive patients with haematological malignancies were enrolled in a study of bleeding data collection during the period of thrombocytopenia. A short educational session and information sheet was designed for self‐assessment. Platelet counts and all transfusions were recorded daily. Bleeding scores were translated into World Health Organization (WHO) bleeding grades. Results Nineteen patients were included in the study. Four‐hundred and ten days of thrombocytopenia were eligible for assessment of bleeds. Self‐assessment was feasible, as defined by the total proportion of days on which self‐assessment was completed (70%, 288 thrombocytopenic days). There was 86% agreement between bleeding data collected by self‐assessment and by medical examination using a structured assessment form. Examples of discrepancies included the duration of petechiae/bruises and the reporting of minor bleeding. There was no evidence for an association between patients’ morning platelet count and daily WHO bleeding grade. The incidences of WHO grade 1 and grade 2 bleeding on days with platelet counts ≤ 10 × 10⁹/l, 11–20 × 10⁹/l, and > 20 × 10⁹/l were similar and did not reveal higher rates of bleeding at lower counts. Conclusions Patient self‐assessment can help to support comprehensive daily prospective monitoring of bleeding, specifically facilitating data collection following hospital discharge. The discrepancies between self‐assessment and medical examination highlight the need to develop a validated international assessment tool. The association among platelet count, risk of bleeding and role of prophylactic platelet transfusions needs further evaluation in larger prospective trials.     

Romiplostim for the management of perioperative thrombocytopenia

Thrombocytopenic patients requiring invasive surgery have few options to improve their platelet count preoperatively. This is a single‐centre, retrospective review of thrombocytopenic patients receiving the thrombopoietin receptor agonist romiplostim perioperatively to allow for surgical interventions. Patient characteristics, romiplostim use, and surgical and safety outcomes (bleeding, thrombosis, transfusions) were collected and analysed. Forty‐seven patients underwent 51 surgical procedures (ranging from total hip arthroplasty to open cardiac surgery) with romiplostim support. Thrombocytopenia aetiologies included immune thrombocytopenia, chronic liver disease, haematological malignancy, drug‐related thrombocytopenia, and hereditary thrombocytopenia. Median (range) platelet counts improved, from 47 × 10⁹/l (9–120 × 10⁹/l) at romiplostim initiation to 164 × 10⁹/l (28–603 × 10⁹/l) at the time of surgery (P < 0·0001). A dose of 3 μg/kg per week for 2 doses increased the platelet count to >100 × 10⁹/l in 79% of patients within 14 days. In 96% of cases, surgery proceeded on schedule without delay or cancellation. Four patients had bleeding events unrelated to thrombocytopenia and 1 patient developed deep venous thrombosis. Six patients required red cell transfusion and 3 patients required platelet transfusion perioperatively. In conclusion, romiplostim was effective in increasing platelet counts to allow surgery to proceed safely and on schedule. Bleeding and thromboembolic events were within acceptable limits for this surgical population.     

Danazol for the treatment of thrombocytopenia in patients with myelodysplastic syndrome

Thrombocytopenia is a poor prognostic indicator in the myelodysplastic syndromes (MDS). Treatment options for patients with symptomatic thrombocytopenia are limited. Danazol, an attenuated androgen, may have some efficacy in increasing the platelet count of patients with MDS. We retrospectively reviewed 33 patients with primary MDS who were treated with danazol for 6 or more weeks. After 6 weeks on danazol, the mean platelet count increased from 42 x 10(9)/L to 60 x 10(9)/L (P < 0.015), and 25 out of 33 patients (76%) had an increase in their platelet counts. Following 12 weeks of treatment, the mean platelet count increased to 67 x 10(9)/L (P < 0.005), and 21 out of 29 patients (72%) had an increase in their platelet counts. Seven out of nine patients no longer required platelet transfusions because bleeding stopped after 6 weeks on danazol. Mean duration of response was 10 months (range 2-68 months). Responses were seen in all French-American-British (FAB) subtypes and in all International Prognostic Scoring System (IPSS) scores. Therapy was well tolerated. Danazol may be effective in MDS patients who are thrombocytopenic.     

Platelet transfusions in infants with necrotizing enterocolitis

Severe thrombocytopenia (< 50 x 10(9)/L) frequently accompanies advanced necrotizing enterocolitis (NEC). In premature infants with severe thrombocytopenia, despite a paucity of evidence to support the practice, platelet transfusions are commonly used to maintain arbitrary levels of platelet counts in an effort to prevent hemorrhage. However, platelet transfusions contain a variety of bioactive factors, including platelet activating factor (PAF), which can augment systemic inflammatory processes. A growing body of evidence that incriminates PAF in the pathogenesis of NEC has emerged over the past few decades from both animal and human data. Both severe thrombocytopenia and multiple platelet transfusions have been associated with increased mortality, but it is admittedly difficult to differentiate between the effects of the underlying disease and the effects, if any, of the platelet transfusions. In this report, we review the roles of PAF and platelet transfusions in infants with severe NEC.     

Changes in platelet count in uncomplicated and severe falciparum malaria

This study investigated alterations in platelet counts pre- and post-treatment with artemisinin derivatives in uncomplicated and severe falciparum malaria. Serial platelet counts were taken over 4 weeks for 110 uncomplicated and 110 severe falciparum malaria patients admitted to the Hospital for Tropical Diseases during 2005-2008. On admission, prior to treatment, thrombocytopenia was found in 73.6% of uncomplicated falciparum malaria patients and 90.9% of severe falciparum malaria cases. Platelet levels significantly lower in severe malaria cases. Although initial platelet counts were lower than normal in both study groups, they slowly increased significantly over time, and approached normal levels by several weeks post-treatment. No bleeding was evident during treatment, and none of the patients required a platelet transfusion. Platelet transfusions are not required for malaria patients with thrombocytopenia who have no bleeding.