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Vancomycin-dependent antibodies associated with thrombocytopenia and refractoriness to platelet transfusion in patients with leukemia.

Two patients with leukemia experienced profound thrombocytopenia and refractoriness to platelet transfusion during vancomycin treatment. In one patient, withdrawal of drug and administration of platelet transfusions restored platelet counts to near normal levels (approximately 100 x 10(9)/L), however, subsequent challenge with vancomycin due to recurring infection again precipitated severe thrombocytopenia (platelets less than 10 x 10(9)/L) and life-threatening hemorrhagic symptoms. Potent vancomycin-dependent antiplatelet antibodies were detected in the serum of both patients during the refractory period using staphylococcal protein A rosette formation. Employing a monoclonal antibody-antigen capture enzyme-linked immunosorbent assay (ELISA), the patients were found to have vancomycin-dependent IgG antibodies that bound specifically to platelet glycoproteins (GP) IIb and/or IIIa. One of these antibodies failed to react with platelets deficient in GPIIb/IIIa obtained from an individual with Glanzmann's thrombasthenia. These findings provide the first major evidence for drug-dependent antibodies in association with severe thrombocytopenia and refractoriness to platelet transfusion in alloimmunized leukemia patients and, further, provide the first demonstration of vancomycin-dependent antibodies reactive with platelets.

Adult↗

Vincristine-laden platelet transfusion for patients with refractory thrombocytopenia.

BACKGROUND: The aim of the present study was to assess the efficacy of vincristine-laden platelet transfusion for patients with refractory thrombocytopenia. PATIENTS AND METHODS: Twenty evaluable patients who received vincristine-laden platelets for refractory thrombocytopenia were included in this retrospective study. Vincristine (1 mg) was added to the platelets and incubated for one hour prior to transfusion. Serial platelet counts following vincristine-laden platelet transfusion and units of platelets transfused in the week prior to and the week after transfusion of vincristine-laden platelets were evaluated. RESULTS: The underlying diseases of the patients were lung cancer (n =4), breast cancer following autologous hematopoietic stem cell transplantation and acute myeloid leukemia (n=3 each), myelodysplastic syndrome (n=2), acute lymphoid leukemia, chronic lymphoid leukemia, chronic myeloid leukemia, multiple myeloma, ovarian cancer, aspergillosis, cytomegalovirus infection and systemic lupus erythematosus (n = 1 each). The median rate of change of platelet count after transfusion of vincristine-laden platelets was 550/microL/day (range, -1,000 to 12,8001/microL/day; p=0.003). The median change in the number of units of platelets transfused in the week following vincristine-laden platelet transfusion was -1.5 as compared to the week prior to the transfusion (p=0.031). Patients with a primary marrow disorder exhibited no difference in either the rate of change in platelet count or in the difference in the units of platelets transfused compared to those without a primary bone marrow disorder. CONCLUSION: Vincristine-laden platelet transfusion was associated with significantly increased platelet counts and a subsequent decrease in platelet transfusion.

Adult↗

A contribution to the indications for platelet transfusion and determination of its therapeutic efficacy.

The platelet count does not really reflect the true bleeding risk in chronically thrombocytopenic patients. Recently, we reported on two modifications of an in vitro bleeding test (IVBT) which appeared to be suitable for the evaluation of primary non-vascular hemostatis in thrombocytopenic and anemic patients (platelets 10-50,000/microL, hct 16-30 L/L). We report on the clinical study conducted with the IVBT modification which proved to be superior. Fifty thrombocytopenic patients, 42 with bone marrow hypoplasia and 8 with autoimmune thrombocytopenia, were followed up for a total of 686 days and received 161 platelet transfusions (mainly from cell separator). The IVBT was carried out with the Thrombostat 4000 in triplicate using 120 microns filters and evaluating the occlusion time (OT). Additionally, cell count, hematocrit, body temperature, platelet volume, platelet distribution width, Simplate time and a detailed analysis of bleeding signs for the calculation of a bleeding score were performed. The IVBT modification used allowed the determination of platelet-related bleeding risk in thrombocytopenic patients. With the IVBT, significant differences in platelet function in different patients could be demonstrated which primarily reflected the underlying disease. In addition, bone marrow regeneration correlated with platelet function. From the findings of this study, the authors formulate criteria for the indication of platelet transfusion which includes platelet function as well as the platelet count. Increased individual bleeding risk factors have to be considered too. But before generalization these criteria have to be verified by a controlled prospective study.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Tests↗

Analysis of the kinetics of TPO uptake during platelet transfusion.

BACKGROUND: It has been shown in several studies that platelets play a role in the removal of TPO from the circulation. For instance, in vitro studies have shown that platelets can bind and internalize TPO, and transfusion studies have shown that the concentration of circulating TPO decreased after platelet transfusion. In the current study, the in vivo kinetics of plasma TPO levels and TPO uptake by transfused platelets is analyzed in more detail. STUDY DESIGN AND METHODS: Serial blood samples from patients who received a platelet transfusion were analyzed with respect to platelet count, plasma TPO concentration, and TPO content per platelet. In addition, the capacity of transfused platelets to bind TPO in vitro was assessed. RESULTS: Platelet counts increased immediately after transfusion, but subsequently started to decrease. Conversely, TPO levels decreased significantly but then returned to baseline level by 44 hours after transfusion. Platelet count and plasma TPO concentration were inversely correlated (r(p) = -0.9; p<0.05). The decrease in TPO concentration upon transfusion was accompanied by a significant increase in the platelet-associated TPO concentration. After transfusion, platelets isolated from the patient still displayed functional TPO receptors, as indicated by their intact capacity to bind TPO in vitro. CONCLUSION: The decrease in plasma TPO followed by the increase in platelet TPO provides evidence that platelets are responsible for the clearance of TPO in circulation. In vivo, platelets can bind and may degrade TPO upon platelet transfusion.

Humans↗

Platelet transfusion therapy for medical and surgical patients.

Platelet transfusions have become more common as more patients undergo bone marrow transplantation and aggressive chemotherapy for malignant diseases. This paper reviews the indications for platelet transfusions and the factors that can decrease their effectiveness.

Contraindications↗

Factors influencing 20-hour increments after platelet transfusion.

The 20-hour posttransfusion platelet count determines transfusion policy for patients requiring platelet support, and yet factors influencing the 20-hour count have been poorly defined. The clinical factors influencing both the 1- and 20-hour corrected count increment (CCI), were studied in 623 human leukocyte antigen (HLA)-unmatched platelet transfusions in 108 patients. The 1- and 20-hour CCIs were highly correlated (r = 0.67, p less than 0.001). On average, the 20-hour CCI was 64 percent of the 1-hour CCI. Multiple linear regression analyses identified splenectomy, bone marrow transplantation, disseminated intravascular coagulation, administration of amphotericin B, palpable spleen, and HLA antibody grade as the major factors influencing the 20-hour posttransfusion CCI. Platelet-specific antibodies, number of concurrent antibiotics, clinical bleeding, and temperature did not significantly influence the 20-hour posttransfusion CCI. The 1-hour CCI was the only significant factor influencing the 20-hour CCI in a regression model containing the 1-hour CCI and the above factors. Thus, the same clinical factors exert a major influence on the CCI at both 1 and 20 hours after platelet transfusion, with no evidence that any factor has more influence at 20 hours after transfusion than at 1 hour.

Blood Platelets↗

A risk model for thrombocytopenia requiring platelet transfusion after cytotoxic chemotherapy.

Severe thrombocytopenia is a rare but life-threatening side effect of cytotoxic chemotherapy for which risk factors are not well known. Our objective was to delineate a risk model for chemotherapy-induced thrombocytopenia requiring platelet transfusions in cancer patients. Univariate and multivariate analysis of risk factors for chemotherapy-induced thrombocytopenia requiring platelet transfusions were performed on the cohort of the 1,051 patients (CLB 1996) treated with chemotherapy in the Department of Medicine of the Centre Léon Bérard (CLB) in 1996. In univariate analysis, performance status (PS) greater than 1, platelet count less than 150, 000/microL at day 1 (d1) before the initiation of chemotherapy, d1 lymphocyte count < or = 700/microL, d1 polymorphonuclear leukocyte count less than 1,500/microL, and the type of chemotherapy (high risk v others) were significantly associated (P < .01) with an increased risk of severe thrombocytopenia requiring platelet transfusions. Using logistic regression, d1 platelet count less than 150,000/microL (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.9 to 9.6), d1 lymphocyte counts < or = 700/microL (OR, 3.37; 95% CI, 1.77 to 6.4), the type of chemotherapy (OR, 3.38; 95% CI, 1.77 to 6.4), and PS greater than 1 (OR, 2.23; 95% CI, 1.22 to 4.1) were identified as independent risk factors for platelet transfusions. The observed incidences of platelet transfusions were 45%, 13%, 7%, and 1.5% for patients with > or = 3, 2, 1, or 0 risk factors, respectively. This model was then tested in 3 groups of patients treated with chemotherapy used as validation samples: (1) the series of 340 patients treated in the CLB in the first 6 months of 1997, (2) the prospective multicentric cohort of 321 patients of the ELYPSE 1 study, and (3) the series of 149 patients with non-Hodgkin's lymphoma treated in the CLB within prospective phase III trials (1987 to 1995). In these 3 groups, the observed incidences of platelet transfusions in the above-defined risk groups did not differ significantly (P > .1) from those calculated in the model. This risk index could be useful to identify patients at high risk for chemotherapy-induced thrombocytopenia requiring platelet transfusions.

Adult↗

Transfusion-related acute lung injury (TRALI) following platelet transfusion in a patient receiving high-dose interleukin-2 for treatment of metastatic renal cell carcinoma.

Transfusion-related acute lung injury (TRALI) is an uncommon life-threatening complication of hemotherapy. It is hypothesized to be the result of two independent insults: the first related to the clinical status of the patient and the second to the infusion of biologic response modifiers within blood components. We present a case of TRALI in a patient who received high-dose Interleukin-2 (IL-2) as treatment for metastatic renal cell carcinoma, where IL-2 is speculated to have been the first insult and transfusion of platelet concentrate the second. This is the first reported case of TRALI complicating treatment with high-dose immunotherapy.

Blood Platelets↗

Influence of clinical status on the efficiency of stored platelet transfusion.

The efficiency of stored platelet transfusion was evaluated in terms of clinical status in 141 thrombocytopenic patients. In a paired prospective study in which fresh platelets were used as controls, clinical efficiency was assessed on the basis of the ability to increase platelet count (recovery) and the time to the next transfusion (D). In 48 clinically stable patients, recovery of fresh and stored platelets was similar (47% and 41%, respectively) and the interval to the next transfusion was D4 and D3. In contrast, 27 patients who had bacterial infections showed significantly different recoveries (24%/5%) and the interval to the next transfusion was D3/D1 for fresh and stored platelets respectively. Similarly, in 16 patients who were treated concurrently with amphotericin B, 18 other patients with graft-versus-host disease, nine with splenomegaly and four with veno-occlusive disease (VOD), fresh platelets performed better than stored platelets, showing recoveries of 27%/18%, 29%/15%, 16%/3% and 15%/2%. Furthermore, the need for retransfusion within 24 h was significantly increased with stored platelets. In 19 patients with anti-HLA alloimmunization who were transfused with HLA-matched fresh and stored apheresis platelet concentrate (APC), efficiency was similar (38%/36% and D4/D3). This study indicates that the storage induces an impressive decrease in the in-vivo platelet recovery and survival in patients with certain clinical conditions.

Adult↗

Addition of platelet transfusions to corticosteroids does not increase the recovery of severe HELLP syndrome.

OBJECTIVE: The objective was to evaluate the effect of dexamethasone and platelet transfusion treatment on recovery in patients with class 1 hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. MATERIAL AND METHODS: All women with class 1 HELLP syndrome (true HELLP syndrome) who were seen at the hospital Complejo Hospitalario de la Caja de Seguro Social de Panama, Panama between July 1996 and June 2004 took part in a retrospective, comparative study. They were divided into two groups. One group received dexamethasone and the other group received dexamethasone plus platelet transfusion. True HELLP syndrome was defined as hemolysis, elevated liver enzymes, and maternal platelet nadir < or =50,000 platelets/microl. MAIN OUTCOME MEASURE: The primary endpoint was resolution of the HELLP syndrome as recognized by normalization of the platelet count (> or =150,000/microl) and the mean length (measured in days) of the postpartum stay in hospital. RESULTS: Forty-six women with true HELLP syndrome were studied. Twenty-six patients received dexamethasone and 20 received dexamethasone plus platelet transfusion. The normalization of the platelet count was significantly more rapid in the dexamethasone group (p<0.004) and the postpartum hospital stay was significantly more prolonged in the dexamethasone plus platelet transfusion group (p<0.02). There was no maternal death. CONCLUSIONS: The findings suggest the initiation of high-dose dexamethasone therapy in women with true HELLP syndrome, with the next step being delivery, and probably platelet count < or =50,000/microl alone is not always an indication for platelet transfusion.

Adult↗

Alloimmunization following platelet transfusion: the absence of a dose-response relationship.

A major concern about the use of prophylactic platelet transfusions is the development of alloimmunization. To determine whether the rate of alloimmunization is related to the number of platelet transfusions, we measured the development of lymphocytotoxic antibody in the first 2 mo of induction therapy in patients with acute nonlymphocytic leukemia. All patients received prophylactic random donor platelets and packed red blood cells during induction. No patient had lymphocytotoxic antibody present at admission. One hundred and six patients received an average of 9.3 platelet transfusions (range 2-34) containing an average of 61 U (range 9-236). The rate of alloimmunization was 38% overall and correlated with refractoriness to platelet transfusions. Ten of 19 patients receiving less than or equal to 4 transfusions became immunized, compared with 30/87 patients receiving less than 4 transfusions. There was no relationship between the number of platelet transfusions given and the rate of severity of alloimmunization, suggesting prophylactic platelets need not be withheld expressly to prevent alloimmunization.

Adult↗

[Influence of clinical status on the efficacy of stored platelet transfusion].

The efficiency of stored platelet transfusion was evaluated in terms of clinical status in 136 thrombocytopenic patients. In a paired prospective study in which fresh platelets were used as controls, clinical efficiency was assessed on the basis of the ability to increase platelet count (recovery) and the interval to the next transfusion (D). In 48 clinically stable patients, recovery of fresh and stored platelets was similar (47% and 41% respectively) and the interval to the next transfusion was D4 and D3. In contrast, 27 patients who had bacterial infections showed significantly different recoveries (24%/5%) and the interval to the next transfusion was D3/D1 for fresh and stored platelets respectively. Similarly, in 16 patients who were treated concurrently with Amphotericin B, 18 other patients with graft-versus-host disease, 5 with splenomegaly and 3 with veno-occlusive disease (VOD), fresh platelets performed better than stored platelets, showing recoveries of 27%/18%, 29%/15%, 15%/1%, 22%/3%. Furthermore, the need for retransfusion within 24 hours was significantly increased with stored platelets. In 19 patients with anti-HLA allo-immunization who were transfused with HLA-matched fresh and stored APC, efficiency was similar (38%/36% and D4/D3). This study indicates that the storage has a major detrimental effect on platelet recovery and survival in patients with certain clinical conditions.

Adolescent↗

The effects of splenectomy on engraftment and platelet transfusion requirements in patients with chronic myelogenous leukemia undergoing marrow transplantation.

Granulocyte and platelet recovery as well as platelet transfusion requirements following allogeneic marrow transplantation were analyzed in 67 patients with chronic myelogenous leukemia in the chronic phase. Twenty patients had splenectomy prior to transplantation. Forty-seven patients were transplanted without splenectomy, 21 of whom had splenic enlargement by physical examination. There were no differences in the proportion of patients with granulocyte recovery, but the recovery of peripheral granulocytes to levels of 200, 500 and 1,000/mm3 occurred more rapidly in the splenectomy group than in the no-splenectomy group. Patients with splenectomy received platelet transfusions for a mean of 10 (2-36) days as compared to 20 (3-82) days for patients without splenectomy (p less than .001). Eighteen (90%) patients with splenectomy became platelet transfusion independent at a median of 16 (2-32) days after transplantation as compared to 40 (85%) patients without splenectomy who became transfusion independent at a median of 28 (15-86) days (p less than .001). The proportion of patients achieving platelet levels of 50 and 100 X 10(3)/mm3 did not differ between the two groups (p = .07), but patients in the splenectomy group achieved these levels more rapidly following transplant (p less than .001). One of 17 evaluable patients in the splenectomy group and 31 of 46 in the no-splenectomy group became refractory to random platelets (p less than .001) and required platelets from family members or unrelated completely or partially HLA matched donors. In the no-splenectomy group, splenic size did not affect the speed of granulocyte or platelet recovery or platelet transfusion requirements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Ex-vivo bleeding time as a control for platelet transfusion].

Thrombocytopenia is the most common cause of bleeding tendency and, if due to impaired platelet production, is best treated by platelet transfusion. For patients with acute leukemia prophylactic platelet transfusion should be considered if platelet count is below 20 x 10(9)/l. This will be underlined by a retrospective analysis at our clinic of 231 patients suffering from acute myelocytic leukemia (AML FAB M1-7) and showing an early-death rate of 7.7% by bleeding complications. To estimate the effectiveness of platelet transfusions, not only stopping of bleeding symptoms and corrected count increment (CCI) should be taken into account but also whether the patient has fever, sepsis, hepato-splenomegaly or has taken special drugs. Measuring the in vivo bleeding time is of little use for low reproduction and is stressing for patients. In 1985 Kratzer described a new and sensitive method for the evaluation of platelet function. After modifying this method it is now possible to test platelet function even with platelet counts below 50 x 10(9)/l.

Bleeding Time↗

Refractoriness to platelet transfusion.

This review discusses the causes of refractoriness to platelet transfusions and presents three options for its management. Platelet refractoriness is a complication of platelet transfusion that affects variable proportions of patients, mostly depending on their diagnosis, previous immunologic stimuli, and type of blood products used for transfusion. A large recent study showed that platelet refractoriness develops in 13% of patients with acute leukemia transfused with traditional blood products and in 3 to 4% of recipients of white cell-reduced blood components. Options to manage platelet refractoriness include platelets from HLA-typed donors, platelet cross-matching, and the antibody specificity prediction method. The selection of the most convenient approach depends on local skills and the available economic and organizational resources. Finally, emerging concepts are presented which could impact the management of platelet refractoriness.

Histocompatibility Testing↗

The behavior of transfused platelets in dengue hemorrhagic fever.

The transfusion of platelet concentrate has been proved as a valuable clinical procedure in the management of bleeding in dengue hemorrhagic fever (DHF). This paper described the behavior of transfused platelets as platelet response and platelet increment in DHF patients with and without shock. Fifteen patients with DHF were studied, aged 2 to 12 years old. All had bleeding manifestation, ie GI, skin, nose or gum. Fresh human platelet concentrate was transfused to 5 non-shock cases and 10 shock cases with different dosages as the low dose (0.15-0.23 U/kg) and high dose (0.28-0.46 U/kg). The cessation of active bleeding was noted by clinical observation or hematocrit determination. The degree of elevation of the circulating platelets tended to vary inversely to the degree of shock and directly to the amounts of platelets infused. The survival of transfused platelets was very short in shock cases, about few hours to one day. This may be due to many factors: platelet plug to injured vessels, immune complex reaction, trapping of platelets to the poor circulation area, rapid utilization and destruction of platelets by injured vessels or virus and slow circulation promoting platelet adhesion.

Child↗

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.

Enterocolitis, Necrotizing↗