Dr Meera Chitlur explores diagnosing Glanzmann’s thrombasthenia, and the roles of platelet transfusions and rFVIIa in treating emergent bleeds.
Hello i’m dr meera chitlur a professor of pediatrics at wayne state university school of medicine and a physician in the division of hematology oncology at children’s hospital of michigan in detroit welcome to our program about glancements from athenia sponsored by novo nordisk klan smith thromasthenia is a rare bleeding disorder characterized by impaired platelet
Function that was first described by edward glansman’s a swiss pediatrician in 1918. glassenia is an inherited autosomal recessive disorder caused by mutations in the gp2b3a integrine receptor on platelets it has an incidence of approximately one in one million and can affect both males and females and is reported to be common in ethnic groups that display high
Instances of consanguinity such as iraqi jews certain palestinian arab populations and french gypsies patients with glancements thrombosthenia develop symptoms early in childhood bleeding episodes are typically mucocutaneous most commonly presenting with epistaxis gingival bleeding and heavy menstrual bleeding in women epistaxis is more severe and frequent among
Children however symptoms related to epistaxis tend to decline as the patients approach adulthood heavy menstrual breeding is common and can be severe among girls and women here we’ll review the diagnostic algorithm of how klansman’s rhombusthenia is diagnosed in patients with a personal or family history suggestive of a bleeding disorder a complete blood count
With a smear review is conducted along with basic coagulation tests if the pt aptt and platelet count are normal further studies should be conducted bond willebrand factor testing should be performed prior to or concurrently with platelet aggregation studies a platelet function analyzer can be used as a screening test the assay contains collagen and adp and collagen
And epinephrine embedded cartridges that mimic a damaged vessel endothelium when whole blood is added platelet adhesion activation and aggregation results in plugging of the aperture which is recorded as the closure time in patients with glasmus rhombusthenia the closure time is prolonged the diagnosis of glancements rhombusthenia can then be confirmed to platelet
Aggregation studies which will show absent aggregation with all agonists except restocietin additionally sequence analysis of itg2b and itgb3 genes can be used to confirm diagnosis by identifying mutations that cause classmates from asthenia it is important to be aware of the limitations of the standard treatment and platelet transfusions platelet transfusions
Are the standard of care for severe bleeding episodes and during surgery such that approximately 75 percent of patients have received blood and or platelet transfusions at least once in their lifetime although standard of care in these settings there are risks and limitations to political transfusions for example healthcare providers are required to administer the
Transfusion which must be done at a hospital or clinic platelets have an extremely limited shelf life of five to seven days transmission of bacterial and viral infections is possible there is a possibility of immunologic transfusion reactions platelet aloe immunization can occur when using platelet transmission therapy with possible refractions to future platelet
Transfusions with approximately 50 percent of patients developing anti-platelet antibodies and or develop refractions to platelets and in women of childbearing age there is the possibility of platelet antibodies transferred across the placenta which can harm the fetus indications in usage novo 7 rt coagulation factor 7a recombinant is a coagulation factor indicated
For treatment of bleeding episodes and perioperative management in adults and children with hemophilia a or b with inhibitors congenital factor 7 deficiency and glandsman’s thrombosthenia with refractoriness to play the transfusions with or without antibodies to platelets treatment of bleeding episodes and perioperative management in adults with acquired hemophilia
Important safety information warning thrombosis serious arterial and venous thrombotic events following administration of nova 7rt have been reported discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive nova 7rt monitor patients for signs or symptoms of activation of the coagulation system and for
Thrombosis in the next section i’ll cover the use of nova 7 rt coagulation factor 7a in patients with glasmus rhombusthenia with refractoryness to platelet transfusions with or without antibodies to platelets the patient is a six-year-old monk female diagnosed with glasmus rhombusthenia shortly after birth due to extensive bruising she has a history of hypotensive
Episodes needing icu care with two previous episodes of epistaxis the patient’s airways are scarred from nasal packing due to prior epistaxis episodes and the patient has had previous platelet transfusions with no known platelet refractiveness or antibodies the patient presented to the emergency department with severe epistaxis that started at 5 am and continued
For four hours she appeared lethargic with active bleeding from the right neries and had elevated pulse and slightly low blood pressure her hemoglobin level was 7 grams per deciliter with a normal ptt and normal platelet count the patient was initially treated with tranexamic acid 10 milligrams per kilogram ivq 6 hours and her nose was packed with hemostatic
Matrix she received a packed red blood cell to increase her hemoglobin however her bleeding did not stop and so a platelet transmission was initiated the platelet transmission failed which indicated that the patient was refracted to platelets therefore treatment with novo 7 rt at 90 micrograms per kilogram was initiated q2 hours for three doses and then q4 hours
For two doses following treatment with nova 7 rt hemostasis was achieved to summarize this case epistaxis is the most common cause of severe bleeding and glancements thrombosthenia platelet transfusions are used to stop bleeding when local measures and anti-federal analytics fail patients may become refractory to platelet transfusions and may develop allo antibodies
Against glycoprotein to b3a or hla novo 7 rt is used to achieve hemostasis in patients with glancements thrombosthenia with refractiveness to platelet transfusions with or without antibodies to platelets novo 7 rt is indicated for patients with glasmus rhombusthenia with refractionous to platelet transfusions with or without antibodies to platelets patients who
Receive platelet transfusions are at risk of developing refractions to future transfusions and or platelet antibodies patients with refractiveness to platelet transfusions both those with and without antibodies to platelets may be candidates for novo 7 rt treatment novo 7 rt is the only recombinant factor product approved for the treatment of bleeding episodes in
Patients with glancements thrombosthenia overall treatment with novo 7 rt was successful in 94.4 percent of bleeding episodes and 99.4 percent of surgical procedures adjudicator rated efficacy was consistent across treatment regiments bleeds and surgery types age and refractory and antibody status treatment with nova 7 rt was successful in patients with clinical
Refractoriness with or without platelet-specific antibodies in 94.9 percent of leading episodes and 98.6 percent of surgical procedures in patients without refractiveness or platelet-specific antibodies treatment with nova 7 rt was comparable to treatment with platelets nova 7 rt has a well-established safety profile that comes from experience safety data from
Patients with glasmus romestinia were collected from the glancements from a senior registry and the hemostasis and thrombosis research society registry and in both these registries 140 patients with glasmus rhombusinia received novo 7 rt for 518 bleeding episodes surgeries or traumatic injuries among these patients the incidence of thrombotic events was less than
0.2 percent adverse reactions reported included deep vein thrombosis in one patient headache in two fever and two nausea and one and dyspnea n1 contributing to the safety profile is the fact that novo 7 rt is a recombinant agent with only activated factor 7 in the formulation it is not made from human serum or human proteins let’s review the dosing for nova 7 rt
Nova 7 rt can be infused in two to five minutes it is available in single-use vials and once reconstituted its concentration is one milligram per milliliter or 1000 micrograms per milliliter for acute bleeding episodes the dosing is 90 micrograms per kg every two to six hours until hemostasis is achieved for perioperative management it is administered at a dose of
90 micrograms per kilogram immediately before surgery and can be repeated every two hours for the duration of the procedure both surgically it is administered at a dose of 90 micrograms per kg every two to six hours to prevent post-op bleeding important safety information warning thrombosis serious arterial and venous thrombotic events following administration of
Nova 7rt have been reported discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive nova 7rt monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis warnings and precautions serious arterial and venous thrombotic events have been reported in clinical trials
In post-marketing surveillance patients with congenital hemophilia receiving concomitant treatment with apcc’s activated prothropin complex concentrates older patients particularly with acquired hemophilia and receiving other hemostatic agents and patients with a history of cardiac and vascular disease may have an increased risk of developing thrombotic events
Hypersensitivity reactions including anaphylaxis can occur with novo 7rt patients with a known hypersensitivity to mouse hamster or bovine proteins may be at a higher risk of hypersensitivity reactions discontinue infusion and administer appropriate treatment when hypersensitivity reactions occur factor 7 deficient patients should be monitored for prothrombin time
Pt and factor 7 coagulation activity f7c if f7c fails to reach the expected level or pt is not corrected or bleeding is not controlled after treatment with the recommended doses antibody formation may be suspected and analysis for antibodies should be performed laboratory coagulation parameters ptinr aptt f7c have shown no direct correlation to achieving hemostasis
Adverse reactions the most common and serious adverse reactions in clinical trials are thrombotic events thrombotic adverse reactions following the administration of nova 7rt in clinical trials occurred in four percent of patients with acquired hemophilia and 0.2 percent of bleeding episodes in patients with congenital hemophilia drug interactions thrombosis may
Occur if novo 7rt is administered concomitally with coagulation factor 13. this concludes our presentation thank you for listening
Transcribed from video
Recombinant Factor Therapy Challenges of Treating Glanzmann’s Thrombasthenia (12:07) By Novo Nordisk Factor Therapies