Inherited Giant Platelet Disorder, Kashmiri Thrombocytopenia, a Common Syndrome Found in Srinagar, India

Abstract The causative genetic mutations of inherited giant platelet disorders (IGPD) encompass genes coding for the platelet glycoprotein Ib-IX complex (Bernard Soulier syndrome and its variants), myosin heavy chain 9 (MYH9 gene mutated in May-Hegglin anomaly and other IGPDs), GATA-01 (GATA-related thrombocytopenia), TUBB-1, ITGA2, ITGAB3, FLNA and some others. IGPDs are frequently associated with other disorders including renal disease, sensorineural deafness, and leukocyte inclusion bodies. Most are accompanied with variable degrees of bleeding diathesis, while others, like TUBB1 IGPD, do not have any bleeding manifestations. Harris platelet syndrome (HPS), previously called asymptomatic constitutional macrothrombocytopenia, is an autosomal dominant disorder characterized by low-normal to severe thrombocytopenia IGPD and absence of bleeding. HPS has also been observed in healthy blood donors from the northeastern part of India (Bengal) and some areas of Bangladesh, Bhutan and Nepal. We describe a high prevalence of an autosomal dominantly inherited form of IGPD with mild to severe thrombocytopenia in the Muslim population in Kashmir Valley in the northern Indian subcontinent. 830 voluntary, healthy, male blood donors from Kashmir Valley were included in the study. They were aged 15-55 years (median 31 years) and underwent ancillary screening as follows; CBC, peripheral smear, HBV, HCV, HIV, ANA and Anti-H pylori antibodies. 15% of the donors had thrombocytopenia (mean platelet count 109.6 compared to 189.9 in controls; p=<0.0001). No differences were noted in age between the 2 groups. The mean platelet volume (MPV) in thrombocytopenic subjects was higher (12.53 + 0.78 vs 9.52 + 1.03 fl). The red cell distribution width (RDW) in thrombocytopenic subjects was higher than in those with normal counts (15.6 + 1.61 Vs 13. 22 + 1.36, p=<0.001). Hematocrit and other red cell indices were not different in the 2 groups. None of the participants had a history of bleeding, renal disease, sensorineural deafness, or leukocyte inclusion bodies. Peripheral blood platelet morphology revealed large platelets in all subjects. In a pilot study of 7 families, Kashmiri thrombocytopenia was compatible with autosomal dominant inheritance affecting both genders. The congenital nature of Kashmiri thrombocytopenia was demonstrated by analyses of 34 consecutive neonates born in Sher-i-Kashmir Institute Hospital; among 20 girls and 19 boys, we found 18% (2 male and 5 female) to have low platelet count, the mean platelet count of the affected group when compared to unaffected group were 102.6 vs 234 (p=<0.001) respectively. We then searched for a causative mutation using the following approaches. We sequenced the MYH9 gene and no mutation was found. We then employed SNP array analyses using Shared Genome Segment (SGS) and Whole Genome Association Study (WGAS). We were able to exclude all previously reported IGPD-causing genes. SGS that overlapped with WGAS narrowed the target into 3 chromosome regions in Chr. 5 (rs6872531-rs100072476), Chr. 9 (rs11999541-rs12682912) and Chr. 10 (rs11013452-rs7083349). The performed SNP analyses included large genomic segments as candidates for a Kashmiri thrombocytopenia-causative gene. To further narrow down the cause of this disorder, we recruited 3 TRIO families (an affected parent and a child) for stronger linkage analysis and next-generation sequencing to continue the search for the cause of the Kashmiri thrombocytopenia. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Platelet and Red Blood Cell Indices in Harris Platelet Syndrome.

Blood ◽

10.1182/blood.v108.11.3988.3988 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3988-3988 ◽

Cited By ~ 1

Author(s):

Harris V.K. Naina ◽

Samar Harris

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Blood Donors ◽

Severe Thrombocytopenia ◽

Giant Platelets ◽

Giant Platelet ◽

Normal Platelet ◽

Platelet Disorder ◽

Significant Difference ◽

Blood Cell Morphology

Abstract Inherited giant platelet disorders are a group of rare disorders characterized by thrombocytopenia, giant platelets and variable bleeding symptoms. Naina et al., described a new giant platelet disorder called Harris Platelet Syndrome (HPS), the most common inherited giant platelet disorder occurring in up to one third of blood donors from north eastern part of Indian subcontinent. HPS is characterized by an autosomal dominant mode of inheritance with normal to severe thrombocytopenia (less than 50x109/L), giant platelets (mean platelet volume more than 10fL) and absent bleeding symptoms with normal platelet aggregation studies. Occasionally abnormalities in red blood cell morphology have been associated with certain giant platelet disorders such as stomatocytosis in Mediterranean Macrothrmboctopenia, dyserythropoiesis in GATA 1 associated macrothrombocytopenia and thalassemia, in X Linked Thrombocytopenia Thalassemia (XLTT). This study was undertaken to analyze the platelet and red blood cell indices in blood donors with Harris Platelet syndrome. A total of 203 blood donors were included in this study, 101 blood donors from northeaster part of India with MPV more than 12fl (normal 7–10fl) and 102 blood donors from southern part of India. Before blood donation, all donors were questioned about a history of bleeding conditions, in either themselves or their relatives. Blood samples were collected in ethylenediaminetetraacetic acid (EDTA). Automated platelet counts were performed using a Coulter STKS (Coulter, Hialeah, Florida) within 2 hours of collection. Peripheral blood smears were examined to confirm thrombocytopenia, giant platelets and red blood cell morphology. There was a significant difference between platelet count (Mean ±SD) 136± 40 Vs 262 ± 53 in southern India (p<0.000). Thirty three donors with HPS had a normal platelet count with MPV more than 12fL. MPV was 13.6±0.13 (range 12 to21.9fL) in donors with HPS and 7.3 ±0.6 (range 6–9.2fl) in southern Indian blood donors. The platelet distribution width (PDW) was 17.4±0.8 in donors with HPS and was 16.38±0.5 in southern India blood donors(p<0.000). Though there was a significant difference between hemoglobin, 13.8 ± 1.0 vs and 14.7± 1.1 (P<0.00), there was no significant difference between RDW, MCV, MCH, MCHC. Peripheral blood smear did not show any obvious red blood cell abnormality, but showed giant platelets and thrombocytopenia. Harris platelet syndrome is associated with normal to severe thrombocytopenia, giant platelets and significant platelet anisocytosis. There was no associated red blood cell abnormalities observed with HPS.

Download Full-text

Phase 1/2 Study of AMG 531 in Thrombocytopenic Patients (pts) with Low-Risk Myelodysplastic Syndrome (MDS): Update Including Extended Treatment.

Blood ◽

10.1182/blood.v110.11.250.250 ◽

2007 ◽

Vol 110 (11) ◽

pp. 250-250 ◽

Cited By ~ 22

Author(s):

Hagop Kantarjian ◽

Pierre Fenaux ◽

Mikkael A. Sekeres ◽

Pamela Becker ◽

Adam Boruchov ◽

...

Keyword(s):

Platelet Count ◽

Phase 1 ◽

Blast Cell ◽

Low Risk ◽

Extension Phase ◽

Severe Thrombocytopenia ◽

Platelet Response ◽

Baseline Platelet Count ◽

Cell Counts ◽

The Mean

Abstract Background: AMG 531 is a novel thrombopoiesis-stimulating peptibody that is being studied for its ability to increase platelet production by stimulating the thrombopoietin receptor. This report updates outcomes in Part A of the study as of May 2007 on pts who continued into the extension phase of this ongoing phase 1/2, open-label, sequential-cohort, dose-escalation study to evaluate the safety and efficacy of AMG 531 in low risk MDS pts with severe thrombocytopenia (Kantarjian et al., ASCO, 2007). Methods: Pts with low- risk MDS (IPSS Low or Intermediate-1, excluding CMML), a mean baseline platelet count ≤50×109/L, and only receiving supportive care were eligible to enter this study. Pts were enrolled into sequential cohorts of 300, 700, 1000, and 1500μg, receiving 3 weekly subcutaneous injections of AMG 531. After evaluation of platelet response at week 4, pts could continue AMG 531 in an optional treatment extension at their assigned dose or dose adjust to achieve or maintain a response. Results: The mean duration of exposure to AMG 531 was 23±15.5 (SD) weeks. Of 44 pts enrolled, 40 continued into the extension phase; 16 pts remain on treatment. Eighteen pts (41%) achieved a durable platelet response (per IWG 2006 criteria for at least 8 consecutive weeks). Evaluation of durable responses based on baseline platelet count showed that responses occurred in 12/29 (41%) pts with a baseline count of ≥20×109/L, and in 6/15 (40%) pts with a baseline count of <20×109/L. The mean duration of the platelet response was 22.8±13.3 (SD) weeks. A total of 104 platelet transfusions were given to 17/44 (39%) pts during this study; of these transfusions, 7 were given in 3/18 (17%) pts who achieved a durable response. Treatment-related AEs were reported in 17 pts. There were 3 deaths unrelated to treatment. Two confirmed cases of transformation to AML were reported. These two pts received maximum doses of 300 and 1000μg. Six pts were confirmed to have temporary blast cell increases, three of whom had increases above 20%. Of the 6, 4 were receiving 1500μg and 2 were receiving 1000μg. In all 6 pts, blast cell counts were observed to have fallen upon follow-up assessments within 7 weeks after treatment discontinuation. In one case, treatment was reinitiated at 700μg. Conclusions: In this study, AMG 531 appeared to be well-tolerated in severely thrombocytopenic low-risk MDS pts, and resulted in increased and sustained platelet counts in the responding pts. AMG 531 may have a role in the treatment of low-risk MDS pts who are thrombocytopenic or have a history of bleeding. These data suggest that further exploration is merited in this pt population. Pt recruitment is ongoing until reaching the planned 84 pts.

Download Full-text

Bleeding Complications and Transfusion Threshold in Thrombopenic Patients Receiving Antithrombotic Therapy.

Blood ◽

10.1182/blood.v108.11.962.962 ◽

2006 ◽

Vol 108 (11) ◽

pp. 962-962

Author(s):

Jean-Louis H. Kerkhoffs ◽

Rinie J. van Wordragen-Vlaswinkel ◽

Jeroen C.J. Eikenboom ◽

Anneke Brand

Keyword(s):

At Risk ◽

Platelet Count ◽

Anticoagulant Therapy ◽

Platelet Transfusion ◽

Diagnosis And Treatment ◽

Bleeding Complications ◽

Red Cell ◽

Transfusion Threshold ◽

Risk Of Bleeding ◽

The Mean

Abstract Introduction: Central venous catheters are frequently used in hematooncological patients for the administration of chemotherapy, antibiotics and parenteral feeding. Despite low platelet counts, observed in this category of patients, catheter related thrombosis (VTE), with the need for anticoagulant therapy, still occurs in 9.7% of the patients. Treatment of this complication in our institute consists of the removal of the catheter and anti-coagulant therapy, consisting of conventional heparin or low molecular weight heparin. Although solely based on expert opinion, the generally accepted platelet transfusion threshold of 10 x 109/l is raised to 20 – 40 x 109/l. In our institute a trigger of 30 x 109/l is used. We investigated whether this trigger policy is effective in the prevention of bleeding complications. Methods: We performed a case-control study to study bleeding complications and threshold policy. From 1 February 2000 to 1 May 2005 we reviewed medical records of patients, admitted at the hematology department of the Leiden University Medical Center. A total of 22 patients were identified having thrombosis confirmed by ultrasound or phlebography. The database of a recently performed clinical trial in our institution was used to select a control group. Thirty-one controls were selected, matched for age, gender, diagnosis and treatment. For each patient, we calculated the days at risk of bleeding, i.e. days of thrombocytopenia with or without anti-coagulant therapy and recorded bleeding complications, platelet and red cell transfusions from the medical charts. Statistical analysis was performed using SPSS. Results: There were no significant differences between patients with or without VTE in regard to age, gender, diagnosis and treatment. The number of days at risk of bleeding for patients without VTE was 511 days and for VTE group 239 days. The table shows the number of bleeding complications, the mean platelet count, the mean platelet transfusion threshold and the number of platelet and red cell transfusions. Both univariate as multivariate analysis (including age, gender, diagnosis, treatment and VTE-status) showed a significant effect of the existence of VTE on the occurrence of bleeding complications. The Odds’ ratio of bleeding in the VTE group compared to the non-VTE group was 2.9 (CI 95: 1.7 – 5.0; p = 0.0002). More then 95% of the bleeding complications consisted of WHO grades I and II. No lethal bleeding was observed. Discussion: Patients experiencing (catheter-related) venous thrombosis treated with anticoagulant therapy during a period of thrombocytopenia showed an increased risk of bleeding complications, despite a higher platelet transfusion threshold. Whether steering between Scylla and Charibdis can be facilitated by raising the platelet transfusion threshold remains to established. Study outcome No VTE VTE p value n = number Days at risk 511 239 n bleeding complications per day at risk 0.05 0.13 0.0002 mean platelet count (10E9/l) +/− SD 28 +/− 16 38 +/− 17 < 0.0001 mean platelet transfusion threshold (10E9/l) +/− SD 12 +/− 9 28 +/− 12 < 0.0001 n platelet transfusions per day at risk 0.35 0.49 0.0003 n red cell transfusions per day at risk 0.34 0.41 0.073

Download Full-text

Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome

Blood ◽

10.1182/blood-2002-09-2783 ◽

2003 ◽

Vol 102 (2) ◽

pp. 529-534 ◽

Cited By ~ 30

Author(s):

Samuel Deutsch ◽

Alexandra Rideau ◽

Marie-Luce Bochaton-Piallat ◽

Giuseppe Merla ◽

Antoine Geinoz ◽

...

Keyword(s):

Mrna Stability ◽

Inclusion Bodies ◽

Autosomal Dominant ◽

Protein Localization ◽

Sensorineural Deafness ◽

Nonmuscle Myosin ◽

Giant Platelets ◽

Myh9 Gene ◽

Fechtner Syndrome ◽

Genotype Correlation

AbstractMay-Hegglin anomaly (MHA), Fechtner syndrome (FTNS), Sebastian syndrome (SBS), and Epstein syndrome (EPS) are a group of rare, autosomal dominant disorders characterized by thrombocytopenia, giant platelets, and Döhle-like inclusion bodies, together with variable manifestations of Alport-like symptoms that include high-tone sensorineural deafness, cataracts, and nephritis. These disorders result from mutations in the MYH9 gene, which encodes for the nonmuscle myosin heavy chain A protein (also known as NMMHC-A). To date 20 different mutations have been characterized for this gene, but no clear phenotype-genotype correlation has been established, and very little is known regarding the molecular pathogenesis of this group of diseases. Here, we describe 2 new families with MHA/FTNS phenotypes that have been characterized in terms of their mutations, protein localization in megakaryocytes, protein expression, and mRNA stability. Our findings suggest that, at least for the Asp1424Asn mutation in the MYH9 gene, the phenotypes result from a highly unstable protein. No abnormalities in protein localization or mRNA stability were observed. We hypothesize that haploinsufficiency of the MYH9 results in a failure to properly reorganize the cytoskeleton in megakaryocytes as required for efficient platelet production.

Download Full-text

Outcomes of Referrals for Mild and Moderate Thrombocytopenia

Blood ◽

10.1182/blood.v126.23.41.41 ◽

2015 ◽

Vol 126 (23) ◽

pp. 41-41

Author(s):

Charles Schlappi ◽

David McCall ◽

Prasannalaxmi Palabindela ◽

Christy Bemrich Stolz ◽

Lee Hilliard ◽

...

Keyword(s):

Platelet Count ◽

Chart Review ◽

Univariate Analysis ◽

Retrospective Chart Review ◽

Severe Thrombocytopenia ◽

Platelet Counts ◽

Pediatric Hematology ◽

Normal Platelet Count ◽

Normal Platelet ◽

The Mean

Abstract Thrombocytopenia is a common reason for referral to a Pediatric Hematologist Oncologist. However, the need for acute intervention in patients with mild or moderate thrombocytopenia is likely a rare event. Because mild and moderate thrombocytopenia is less likely to need intervention and could resolve, the potentially stressful impact of referral to an Oncology center needs consideration. But with minimal literature to support the hypothesis that mild to moderate thrombocytopenia is unlikely associated with severe or progressive hematologic diseases, our ability to provide evidence based recommendations for need for referral is limited. To better understand the course for patients with mild and moderate thrombocytopenia, we conducted a retrospective chart review to assess the prevalence, outcomes, and need for intervention among patients referred for thrombocytopenia. Methods: We conducted a retrospective chart review of 1,140 patients referred to a large Pediatric Hematology Oncology program over a three year period (2012-2014). The diagnosis and demographics were recorded for every patient. Platelet counts at time of referral, lowest platelet count, and current platelet count were recorded and categorized as mild (plt: 100-149x103/mL), moderate (plt: 50-99 x103/mL), severe (plt: 20-49 x103/mL), and very severe (plt: <20 x103/mL). Therapeutic interventions and reason for intervention were recorded. Finally, ANA, platelet antibody and IgG levels were recorded. Descriptive statistics and univariate analysis were conducted using JMP10. Results: In a three year period (2012-2014), 1140 patients were referred to Pediatric Hematology Oncology, 902 of these patients for hematologic diagnoses. One hundred and three (11.4%) of 902 Hematology patients were referred for thrombocytopenia. The mean age of patients with thrombocytopenia was 9.2 years (s.d. 5.8yrs) and 58% were male. At the time of referral, 29% were categorized as mild, 33% were moderate, 17% severe and 21% very severe. The mean platelet count was 68 x103/mL (range 3-143). Younger patients had lower platelet counts (p<0.001), but no differences in mean platelet count were identified by gender (F:M 59 vs. 75 x103/mL, p=0.06). Thirty patients were categorized as mild thrombocytopenia at the time of referral. Only 2 (6%) patients needed eventual treatment (Crohn's disease and SLE treated by subspecialist) and 7 (23%) patients had at least one episode of moderate thrombocytopenia. On their most recent platelet count, 17 (57%) patients remained categorized as mild, 1 (3%) was moderate, and 12 (40%) had a normal platelet count. Thirty four patients were categorized as moderate thrombocytopenia at the time of referral. Only 5 (15%) patients needed eventual treatment (3 ITP patients for QOL/bruising/petechiae, one for SLE and one for NAIT) and 4 (12%) patients had at least one episode categorized as severe thrombocytopenia. On their most recent platelet count, 9 (26%) patients remained categorized as moderate, 10 (29%) were mild, and 15 (44%) had a normal platelet count. At time of diagnosis, 9 of 17 (53%) patients with severe thrombocytopenia and 19 of 22 (86%) of patients with very severe thrombocytopenia required interventions. Currently, 19 of the 39 (49%) patients have normal platelet counts. Other known diagnoses for the 103 patients include: rheumatologic diagnoses (n=5), drug induced (n=5), NAIT (n=3), ADP deficiency (n=1), X-linked thrombocytopenia (n=1), HSP (n=1), HIV (n=1), and Crohn's (n=1) Conclusion: Mild and moderate thrombocytopenia does not often progress or require interventions. Pediatricians should evaluate for Rheumatologic disorders in their initial work-up for mild to moderate thrombocytopenia as well as consider medication-induced thrombocytopenia. A safe and cost-effective approach to a patient with mild to moderate thrombocytopenia could be to observe repeat laboratory data (including ANA) in lieu of any other co-morbid condition. This approach could save families time, money, effort, and emotional stress in making appointments at large referral institutions. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Association of the degree of thrombocytopenia with cause of death in patients with atrial fibrillation: the Fushimi AF Registry

European Heart Journal ◽

10.1093/eurheartj/ehab724.0462 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

K Ishigami ◽

S Ikeda ◽

K Doi ◽

Y Hamatani ◽

Y Ide ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Failure ◽

Body Weight ◽

Platelet Count ◽

Cause Of Death ◽

Cardiac Death ◽

Severe Thrombocytopenia ◽

Significant Difference ◽

The Mean

Abstract Background Thrombocytopenia is sometimes found in routine blood tests and is associated with an increased risk of mortality in general population. We have previously reported that atrial fibrillation (AF) patients with thrombocytopenia have a higher mortality than those without thrombocytopenia. However, association of the degree of thrombocytopenia with cause of death in AF patients is unknown. Purpose We aimed to investigate the association of baseline platelet count with cause of death including cardiac death, intracranial death, malignancy, infection, extracranial bleeding death, renal failure death, respiratory failure death and undetermined death. Methods The Fushimi AF Registry was designed to enroll all of the AF patients in Fushimi-ku, Kyoto. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. We started to enroll patients from March 2011, and follow-up data with baseline platelet counts less than 150,000/μL were available in 853 patients by the end of September 2020. We divided them into 3 groups according to baseline platelet level: Mild thrombocytopenia (100,000–149,999/μL, n=703), Moderate thrombocytopenia (50,000–99,999/μL, n=120), and Severe thrombocytopenia (<50,000/μL, n=30). Results In the entire cohort, the mean age was 76 years, 34% were women, the mean body weight and body mass index was 59.3 kg and 22.9 kg/m2, and the median platelet count were 121,000/μL (interquartile range 109,000 to 141,000/μL). Compared to Mild thrombocytopenia, patients with Moderate or Severe thrombocytopenia were more likely to have chronic kidney disease (42.2% vs 54.2% vs 73.3%, p=0.0003), have higher HAS-BLED score (1.90 vs 2.14 vs 2.00, p=0.047) and lower hemoglobin (12.8g/dL vs 11.7g/dL vs 11.2g/dL, p<0.0001) and were less often prescribed anti platelet drugs. Age, sex, body weight, systolic blood pressure, previous stroke, previous major bleeding, hypertension, diabetes mellitus, CHADS2 score and CHA2DS2-VASc score were comparable between three groups. During the median follow-up period, the incidence rate (per 100 person-years) of all-cause death was 6.82 vs 15.27 vs 9.64. (p<0.001) On univariate analysis, the incidence of all-cause death was higher in Moderate group than Mild group. (HR: 2.15; 95% CI 1.61–2.87, p<0.0001), but there was no significant difference between Mild and Severe groups. (HR: 1.44; 95% CI 0.78–2.64, p=0.243). The incidence of cardiac death was comparable between three groups. (Mild vs Moderate: HR 0.65; 95% CI 0.15–2.75, p=0.56, Mild vs Severe: HR 1.11; 95% CI 0.15–8.23, p=0.92) Regarding other causes of death such as intracranial bleeding, extracranial bleeding, malignancy, infection, renal failure, respiratory failure and undetermined cause, there was no significant difference. Conclusion Mortality was higher according to the degree of thrombocytopenia in AF patients, but the cause of death was not different among three groups. FUNDunding Acknowledgement Type of funding sources: None.

Download Full-text

Oral Melphalan, Prednisone, and Lenalidomide for Newly Diagnosed Multiple Myeloma Patients: Kinetics of Neutropenia/Thrombocytopenia and Time to Event Results

Blood ◽

10.1182/blood.v112.11.2768.2768 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2768-2768 ◽

Cited By ~ 2

Author(s):

Antonio Palumbo ◽

Patrizia Falco ◽

Francesca Gay ◽

Paolo Corradini ◽

Claudia Crippa ◽

...

Keyword(s):

Multiple Myeloma ◽

Platelet Count ◽

Adverse Events ◽

Dose Reduction ◽

Neutrophil Count ◽

Severe Neutropenia ◽

Severe Thrombocytopenia ◽

Newly Diagnosed ◽

The Mean ◽

Grade 3

Abstract Background: The association of Melphalan, Prednisone and Lenalidomide (MPR) has shown significant anti-myeloma activity in newly diagnosed Multiple Myeloma (MM) patients. In this phase I/II study, the more frequent adverse events were neutropenia and thrombocytopenia. Non-hematologic toxicities were unusual. Methods: We analyzed the kinetics and risk factors for neutropenia and thrombocytopenia in 21 patients (median age 69 years) who received nine four-week cycles of MPR at the maximum tolerated dose (melphalan 0.18 mg/Kg d 1–4, lenalidomide 10 mg d 1–21, prednisone 2 mg/Kg d 1–4, followed by maintenance period with lenalidomide 10 mg/day for 21 days every 4 weeks). We also up-dated efficacy end-point. At the occurrence of grade-3 neutropenia, G-CSF was administered for 5–7 days. The occurrence of grade-4 neutropenia despite G-CSF administration or any other grade-4 hematological toxicities required withholding of treatment and subsequent dose reduction at the start of the following cycle. A new cycle was allowed if the neutrophil count was >1×109/L and platelet count >50×109/L. A delay of 2 weeks was allowed, a delay beyond 2 weeks required dose reduction and a delay beyond 4 weeks required therapy discontinuation. Results: Grade-3 neutropenia occurred in 38.1% of patients, grade-4 neutropenia in 14.2% of patients, but febrile neutropenia was 9.5%. G-CSF was administered in 42.3% of patients. The mean neutrophil count at the start of each MPR cycle was 2.69 × 109/L (SD 1.4). The mean neutrophil count at nadir (day 15–21) of each cycle was 1.43 × 109/L (SD 1.0). The incidence and depth of neutropenia did not increase with the number of cycles. The mean neutrophil count during maintenance was 2.11 × 109/L (SD 1.0). Grade-3 thrombocytopenia occurred in 14.2% of patients and grade-4 thrombocytopenia in 9.5%; one patient required platelet transfusion. The mean platelet count at the start of each MPR cycle was 174 × 109/L (SD 63.9). The mean platelet count at nadir (day 15–21) of each cycle was 121 × 109/L (SD 56.3). Thrombocytopenia was more pronounced after 9 cycles of treatment. The mean platelet count after 9 cycles was 109 × 109/L (SD 53). The mean platelet count at the end of 6 months of lenalidomide maintenance therapy was 158 × 109/L (SD 79.2). One patient required lenalidomide dose reduction for severe neutropenia. Three patients discontinuated therapy for severe thrombocytopenia and neutropenia. Grade 3–4 hematologic toxicity was more frequent in patients with low baseline neutrophil count and in those with Bence-Jones myeloma. Neutropenic fever (9.5%), cutaneous reaction (9.5%), thromboembolism (4.8%) were the most frequent grade 3–4 non-hematologic adverse events. After a median follow-up of 29.5 months, the median time-to-progression was 28.5 months, the median progression-free survival was 28.5 months and the 2-years overall survival was 90.5%. No death was reported in the first 18 months of treatment. Conclusions: MPR is a promising first line regimen for elderly MM patients. Hematologic adverse events were frequent but manageable with the use of G-CSF.

Download Full-text

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650532 ◽

1996 ◽

Vol 76 (01) ◽

pp. 111-117 ◽

Cited By ~ 10

Author(s):

Yasuto Sasaki ◽

Junji Seki ◽

John C Giddings ◽

Junichiro Yamamoto

Keyword(s):

Blood Flow ◽

Thrombus Formation ◽

Dependent Manner ◽

Red Cell ◽

Cell Velocity ◽

Red Cell Velocity ◽

The Mean ◽

Wall Shear ◽

Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

Download Full-text

Acute and Chronic Changes in Platelet Volume and Count After Cardiopulmonary Bypass Induced Thrombocytopenia in Man

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651061 ◽

1987 ◽

Vol 57 (01) ◽

pp. 55-58 ◽

Cited By ~ 37

Author(s):

J F Martin ◽

T D Daniel ◽

E A Trowbridge

Keyword(s):

Platelet Count ◽

Mean Platelet Volume ◽

Artery Bypass ◽

Bypass Graft ◽

Control Group ◽

Artery Bypass Graft ◽

Platelet Volume ◽

Young Males ◽

The Mean

SummaryPatients undergoing surgery for coronary artery bypass graft or heart valve replacement had their platelet count and mean volume measured pre-operatively, immediately post-operatively and serially for up to 48 days after the surgical procedure. The mean pre-operative platelet count of 1.95 ± 0.11 × 1011/1 (n = 26) fell significantly to 1.35 ± 0.09 × 1011/1 immediately post-operatively (p <0.001) (n = 22), without a significant alteration in the mean platelet volume. The average platelet count rose to a maximum of 5.07 ± 0.66 × 1011/1 between days 14 and 17 after surgery while the average mean platelet volume fell from preparative and post-operative values of 7.25 ± 0.14 and 7.20 ± 0.14 fl respectively to a minimum of 6.16 ± 0.16 fl by day 20. Seven patients were followed for 32 days or longer after the operation. By this time they had achieved steady state thrombopoiesis and their average platelet count was 2.44 ± 0.33 × 1011/1, significantly higher than the pre-operative value (p <0.05), while their average mean platelet volume was 6.63 ± 0.21 fl, significantly lower than before surgery (p <0.001). The pre-operative values for the platelet volume and counts of these patients were significantly different from a control group of 32 young males, while the chronic post-operative values were not. These long term changes in platelet volume and count may reflect changes in the thrombopoietic control system secondary to the corrective surgery.

Download Full-text

Hematological Profile of HIV-Infected Patients on First-Line Highly Active Antiretroviral Therapy and Its Correlation With CD4 Count

International Journal of Recent Surgical and Medical Sciences ◽

10.1055/s-0041-1730257 ◽

2021 ◽

Author(s):

John Jospeh Diamond Princy ◽

Kshetrimayum Birendra Singh ◽

Ningthoujam Biplab ◽

Ningthoukhongjam Reema ◽

Rajesh Boini ◽

...

Keyword(s):

Platelet Count ◽

Antiretroviral Therapy ◽

Hiv Infection ◽

Highly Active Antiretroviral Therapy ◽

Cd4 Count ◽

Total Leukocyte Count ◽

Hiv Patients ◽

Positive Correlation ◽

Highly Active ◽

The Mean

Abstract Introduction Human immunodeficiency virus (HIV) infection is a state of profound immunodeficiency. Disorders of hematopoietic system are a common but often overlooked complication of HIV infection. This can manifest at any stage of the disease but more commonly in the advanced stage with low CD4 count. Anemia is the most common hematological abnormality in HIV patients and prevalence ranges from 1.3 to 95%. As HIV disease progresses, the prevalence and severity of anemia also increase. Hence, this study was undertaken to assess the hematological parameters of HIV-infected patients on highly active antiretroviral therapy (HAART) at different treatment durations with the hope to improve the HAART outcome in HIV patients and its correlation with CD4 count. Methods This prospective longitudinal study enrolled 134 HIV-infected patients admitted to or attending the OPD in the Department of Medicine or Antiretroviral Therapy (ART) Center (Center of Excellence), Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, from 2018 to 2020. Complete hemogram, CD4 count, and other related-blood investigations were studied. Results The mean age of the study population was 39.9 ± 11.04 years. Of the 134 patients, 75 (56%) were males and 59 (44%) were females. Twelve (9%) patients had a history of injecting drug use (IDU). TLE (tenofovir, lamivudine, efavirenz) regimen was started on 112 (83.6%) patients and the majority of them (69/134 [51.5%]) had a CD4 count of 200 to 499 cells/mm3, which increased significantly 6 months after HAART to 99 to 1,149 cells/mm3, with a mean of 445 ± 217 cells/mm3. There were significant improvements in hemoglobin (Hb) levels, total leukocyte count (TLC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) after HAART indicating a positive correlation with CD4 count (p < 0.05). Thrombocytopenia was observed higher after HAART when compared to baseline. There was a positive correlation between platelet count and CD4 count. However, the mean corpuscular volume (MCV) and erythrocyte sedimentation rate (ESR) had a negative correlation with CD4 count. Conclusion The study inferred a strong positive correlation between CD4 and Hb levels, TLC, ANC, ALC, and platelet count after HAART with improvement in these values as CD4 count increases. Specific treatment intervention based on the changes in the immunohematological profile trends can help prevent most of the adverse effects on HIV patients in our community.

Download Full-text