{ "@context": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/context/doc", "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009", "id": "CG-AC:AC1009", "type": "ClinicalActionabilityReport", "metadata": { "schemaLabel": "AC-Sepio.Beta-1 (Unofficial)", "contentVersionId": "27226", "producedAtUTC": "Thu, 10 Sep 2026 19:39:25 -0000", "note": "DISCLAIMER: The SEPIO-inspired schema presented here is an initial prototype for Clinical Actionability curation summaries and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema." }, "description": "JSON-LD representation of ClinGen Actionability Stage 2 report modeled with SEPIO. The hierarchically structured document will include:\n1. Contextual & topic information, such as the **conditions/diseases** and the **genes**.\n2. Categorized **evidence narratives**, with references.\n\t* This content corresponds to the texts within the *Actionability Summary Report*\n4. **Outcome & Intervention** pairs, with **consensus scoring** in 5 dimensions:\n\t1. Outcome Severity\n\t2. Outcome Likelihood\n\t3. Intervention Effectiveness\n\t4. Nature of the Intervention\n\t5. Total (Overall) Score\n\n*( Note: The summary report does not include the **Screening Survey** which led to preparation of the actionability report. )", "condition": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/co", "id": "CG-AC:AC1009/co", "type": "GeneticCondition", "label": "Glanzmann thrombasthenia" }, "outcome": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ou/Severe%20or%20prolonged%20hemorrhage", "id": "CG-AC:AC1009/ou/Severe or prolonged hemorrhage", "type": "Outcome", "label": "Severe or prolonged hemorrhage" } ], "intervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/intv/Infusion%20therapy%20as%20indicated%20by%20hematology%20team", "id": "CG-AC:AC1009/intv/Infusion therapy as indicated by hematology team", "type": "Intervention", "label": "Infusion therapy as indicated by hematology team" } ], "clinicalActionabilityProfile": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/cap", "id": "CG-AC:AC1009/cap", "type": "Assertion", "assertionMethod": "The ClinGen AWG developed a standardized protocol to generate evidence-based profiles of clinical actionability of genes and associated disorders in the form of summary reports and semiquantitative metric (SQM) scores.", "releaseDate": "Wed, 09 Feb 2022 00:00:00 -0000", "releaseNum": "1.0.3", "media": "call" }, "evidenceStatements": { "evidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/en/potgd", "id": "CG-AC:AC1009/en/potgd", "type": "EvidenceNarrative", "narrative": "Glanzmann thrombasthenia (GT) is a rare disorder with an estimated global prevalence of 1/1,000,000, but incidence is significantly higher in some areas (e.g. the prevalence of GT in countries in the Arabian Peninsula ranges from 1/100,000 to 1/400,000). The highest incidence of GT reported is 1/40,000 in the Madinah region of Saudi Arabia.", "evidenceDomainTag": "Nature of the Threat.Prevalence of the Genetic Disorder", "publication": [ "CG-AC:RF002736", "CG-AC:RF002737" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/en/cf", "id": "CG-AC:AC1009/en/cf", "type": "EvidenceNarrative", "narrative": "GT is a moderate to severe hemorrhagic disorder characterized by spontaneous mucocutaneous bleeding and an exaggerated response to trauma or surgical procedures due to defective platelet aggregation. Purpura, easy bruising, epistaxis, gingival bleeding and menorrhagia are the most common clinical features. Iron deficiency anemia is common in children. Gastrointestinal bleeding, hemarthrosis, or central nervous system bleeding (e.g. intracranial hemorrhage [ICH]) may also occur. Bleeding time is prolonged, with normal platelet count, normal platelet morphology, and normal coagulation times. Platelets fail to aggregate, either spontaneously or in response to agonists, except for a potential transient response to ristocetin. The severity of GT is variable, ranging from easy bruising only to fatal hemorrhages. The bleeding phenotype in GT is heterogeneous.", "evidenceDomainTag": "Nature of the Threat.Clinical Features", "publication": [ "CG-AC:RF002736", "CG-AC:RF002737", "CG-AC:RF002738", "CG-AC:RF002739", "CG-AC:RF002740", "CG-AC:RF002741", "CG-AC:RF002733", "CG-AC:RF002742", "CG-AC:RF000679" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/en/nh", "id": "CG-AC:AC1009/en/nh", "type": "EvidenceNarrative", "narrative": "GT can present soon after birth with episodic mucocutaneous bleeding, purpura, petechiae, unprovoked bruising, and excessive bleeding from the umbilical stump or post-circumcision. Major bleeding complications during the neonatal period, such as ICH following delivery are rare. The clinical severity of GT tends to diminish with age, although the bleeding manifestations persist and are life-long. Epistaxis is the most common cause of serious bleeding and is more severe in childhood. Menorrhagia is often persistent and severe, sometimes being critical enough to require transfusion at menarche if not managed with oral contraceptives. Pregnancy in individuals with GT includes an increased risk of both maternal and fetal bleeding. The neonates of affected mothers are at risk of thrombocytopenia as maternal antiplatelet antibodies may cross the placenta, which can result in fatal intrauterine hemorrhage. Postpartum hemorrhage (PPH) may occur 1–2 weeks after delivery. The incidence is higher in communities where consanguineous partnerships are frequent. In France, GT is particularly frequent in the Roma population, mainly represented by the Manouche tribe, with a founder variant estimated to have occurred 300–400 years ago. Although GT can be a severe hemorrhagic disease, the prognosis is excellent with careful supportive care. Death from hemorrhage in diagnosed patients is rare unless associated with trauma or other disease.", "evidenceDomainTag": "Nature of the Threat.Natural History", "publication": [ "CG-AC:RF002736", "CG-AC:RF002738", "CG-AC:RF002739", "CG-AC:RF002740", "CG-AC:RF002741", "CG-AC:RF002733", "CG-AC:RF000679" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/en/ACMI2619", "id": "CG-AC:AC1009/en/ACMI2619", "type": "EvidenceNarrative", "narrative": "Autosomal Recessive", "evidenceDomainTag": "Threat Materialization Chances.Modes of Inheritance", "publication": [ "CG-AC:RF002736", "CG-AC:RF002738", "CG-AC:RF002739", "CG-AC:RF002740", "CG-AC:RF002741", "CG-AC:RF002733", "CG-AC:RF002742", "CG-AC:RF000679" ] } ], "tieredEvidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ten/NOI2761", "id": "CG-AC:AC1009/ten/NOI2761", "type": "TieredEvidenceNarrative", "narrative": "The recommended primary interventions for GT includes topical and/or oral medications, rFVIIa infusions and platelet transfusions. Patients should also avoid certain medications and unnecessary procedures that may cause trauma. Management depends on severity, and may include treatment for acute bleeding episodes and prophylaxis for severe recurrent bleeds or surgical preparation. Continuous infusion of rFVIIa might expose patients to a higher than normal risk of perioperative bleedings and thromboembolic events, though reports of adverse events are rare. The International GTR demonstrated that rFVIIa had a good safety profile in surgical procedures, with only two serious and two non-serious adverse events being reported in 4 rFVIIa-treated patient. The GTR review also found no serious adverse events associated with rFVIIa treated bleeding episodes. The development of platelet-specific antibodies should be minimized by avoidance of platelet transfusions, particularly for minor bleeds such as gingival oozing. Recurrent transfusions may also put patients at a higher risk of virial or bacterial infection. Transfusion-related acute lung injury is another risk of platelet transfusion.", "evidenceDomainTag": "Acceptability of Intervention.Natures of Intervention", "publication": [ "CG-AC:RF002736", "CG-AC:RF002737", "CG-AC:RF002738", "CG-AC:RF002740" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ten/RR2587", "id": "CG-AC:AC1009/ten/RR2587", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "No information on relative risk was found.", "evidenceDomainTag": "Threat Materialization Chances.Relative Risks" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ten/ACPE3890", "id": "CG-AC:AC1009/ten/ACPE3890", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "1", "narrative": "A systematic review of the outcomes of pregnancy in those with a diagnosis of GT found that bleeding during or after delivery was reported commonly and was frequently severe. This included intra-partum bleeding in 61% of the informative case reports, primary PPH in 34% and secondary PPH in 24%.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF002739" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ten/PGM2704", "id": "CG-AC:AC1009/ten/PGM2704", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "For cases with a classic GT phenotype, the success of variant analysis by DNA sequencing of ITGA2B and ITGB3 ranges from 80 to 90%. Rare gain of function variants in ITGA2B and ITGB3 have been associated with a distinct autosomal dominant platelet type bleeding disorder.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF002738" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ten/PGM2705", "id": "CG-AC:AC1009/ten/PGM2705", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "The frequency of GT pathogenic variants in the general population was not identified.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ten/ACPE3889", "id": "CG-AC:AC1009/ten/ACPE3889", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "2", "narrative": "The incidence of menorrhagia in patients with GT ranges from 13% to 100%.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF002736" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ten/ACPE3887", "id": "CG-AC:AC1009/ten/ACPE3887", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "2", "narrative": "A cohort study of 177 patients with GT found that purpura, epistaxis, gingival hemorrhage, and menorrhagia are nearly constant features. The following was found for less common clinical features: gastrointestinal hemorrhage (sometimes associated with angiodysplasia) was reported in 22 of the 177 cases (12%). Hematuria occurred in 10 of the 177 patients (5%). Hemarthrosis is rare, and occurred in five of 177 cases. ICH is unusual; it was reported that three of the 177 cases, two of these were following head trauma.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF002740" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ten/ACPE3888", "id": "CG-AC:AC1009/ten/ACPE3888", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "GT shows complete penetrance, characterized by spontaneous and trauma-related mucocutaneous bleeding with variable expression ranging from easy bruising to fatal hemorrhages.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF002738" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ten/EN2754", "id": "CG-AC:AC1009/ten/EN2754", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Bleeding tendencies can differ considerably between affected persons, even within the same family or ethnic group.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF002738" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ten/CDEC2751", "id": "CG-AC:AC1009/ten/CDEC2751", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "2", "narrative": "Although presentation of GT in the neonatal period is common, symptoms are not usually severe and are generally confined to purpura and petechiae. Children who present with easy bruising are often initially thought to suffer non-accidental injury rather than hereditary bleeding disorders.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF002740" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/ten/REC2046", "id": "CG-AC:AC1009/ten/REC2046", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "1", "narrative": "Affected individuals may escape diagnosis into adulthood. A systematic review of the outcomes of pregnancy in GT documented that, despite the high prevalence of bleeding, the diagnosis of GT was made before pregnancy in only 46% of women.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF002739" ] } ], "tieredRecommendations": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACPM5216", "id": "CG-AC:AC1009/tr/ACPM5216", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "A systematic review found that out of patients that used platelet transfusion alone before delivery as prophylaxis against PPH, 38% still experienced PPH compared to 63% of women who received no prophylaxis.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002739" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACPM5219", "id": "CG-AC:AC1009/tr/ACPM5219", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Due to the risk of potentially life-threating maternal or fetal hemorrhage, pregnancy and delivery in patients should be managed by multi-disciplinary teams in centers with clinical expertise in GT and with access to specialist pro-hemostatic therapies. Pregnancy management recommendations include:\n• Tranexamic acid should be given from the onset of established labor and continued regularly through the postpartum period until lochia is minimal. \n• HLA-matched platelet transfusions and/or recombinant factor VIIa should be given prophylactically, at delivery, for patients with a history of bleeding. Repeat doses may be required depending on the clinical picture.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002736", "CG-AC:RF002740", "CG-AC:RF000679" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACPM5215", "id": "CG-AC:AC1009/tr/ACPM5215", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Platelet transfusions are the gold standard treatment for uncontrolled bleeding in GT, preferably, human leukocyte antigen (HLA)-matched single-donor and leukocyte-reduced apheresis platelets. However, any life-threatening bleeding should be treated with platelet transfusions without necessarily waiting for HLA-selected platelets where this would cause delay.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002736", "CG-AC:RF002740", "CG-AC:RF002743" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACPM5217", "id": "CG-AC:AC1009/tr/ACPM5217", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Antifibrinolytic agents, such as epsilon-aminocaproic acid and tranexamic acid, have shown effectiveness in controlling surgical and nonsurgical bleeds, particularly oral bleeds and menorrhagia. Tranexamic acid should be continued for at least 2-week post-delivery due to the increased risk of PPH.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002736", "CG-AC:RF002740" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACPM5214", "id": "CG-AC:AC1009/tr/ACPM5214", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "If bleeding is mild or moderate, treatment with local measures and antifibrinolytic drugs may suffice, especially if the bleeding is mucocutaneous. Local measures may include: compression, use of gelatin sponge or gauze dipped in tranexamic acid, topical thrombin applied to superficial wounds, etc.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002736", "CG-AC:RF002740", "CG-AC:RF002743" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACPM5218", "id": "CG-AC:AC1009/tr/ACPM5218", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "The use of oral contraceptives/hormonal therapy can regulate menstruation in patients with menorrhagia.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002736", "CG-AC:RF002740" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACSU3544", "id": "CG-AC:AC1009/tr/ACSU3544", "type": "TieredRecommendation", "evidenceSourceTier": "Not provided", "recommendation": "Information on surveillance recommendations was not identified.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACCA3213", "id": "CG-AC:AC1009/tr/ACCA3213", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "If the baby is at risk of homozygous GT or fetomaternal alloimmune thrombocytopenia, restrictions to delivery should be applied, as for all babies at risk of ICH. This includes avoidance of ventouse, midcavity forceps, vacuum extraction, FSE and fetal scalp sampling.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF000679" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACCA3216", "id": "CG-AC:AC1009/tr/ACCA3216", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "During pregnancy, blood and platelet transfusion in patients with GT should be avoided wherever possible due to the associated risk of formation of isoantibodies and the potential for alloimmunization.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002736", "CG-AC:RF002744" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACCA3214", "id": "CG-AC:AC1009/tr/ACCA3214", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Procedures such as dilation and curettage, laparoscopy, and endometrial biopsy may worsen blood loss and may lead to hysterectomy, and should be avoided.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002736" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACCA3215", "id": "CG-AC:AC1009/tr/ACCA3215", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Multiple guidelines note that regional anesthesia, particularly central neuraxial anesthesia, may be contraindicated in patients with GT and severe platelet dysfunction.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002736", "CG-AC:RF002740", "CG-AC:RF000679", "CG-AC:RF002744" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACCA3212", "id": "CG-AC:AC1009/tr/ACCA3212", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "GT patients should avoid agents that may cause platelet dysfunction, such as acetylsalicylic acid (aspirin). Nonsteroidal anti-inflammatory agents should be used with caution.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002736", "CG-AC:RF002740" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/REC2817", "id": "CG-AC:AC1009/tr/REC2817", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Treatment by platelet transfusion can become ineffective due to naturally occurring anti-HLA antibodies that may be produced when the patient’s immune system is exposed to exogenous platelets (e.g. after transfusion, during pregnancy). A handful of case studies have found the development of antiplatelet antibodies in 25% to 80% of patients with GT, generally after platelet transfusion treatment. Antibodies may develop more frequently in homozygous patients or in certain founder variant populations. Platelet refractoriness has been reported in about 50% of patients with anti-HLA antibodies.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002736" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/REC2818", "id": "CG-AC:AC1009/tr/REC2818", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "The International Glanzmann Thrombasthenia Registry (GTR), published in 2015, studied 184 patients with 829 bleeding episodes and 96 patients with 206 surgical interventions. rFVIIa alone was used in 124/829 bleeds and the proportion of successful treatment to stop bleeding was 91%. In patients without antibodies/refractoriness, rFVIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for 24 minor and 4 major procedures. The lowest effectiveness of rFVIIa treatment alone was 88.9% (16/18 effective minor procedures) in refractory patients with platelet antibodies.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002736" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACPM5220", "id": "CG-AC:AC1009/tr/ACPM5220", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Desmopressin (DDAVP) may be considered as an additional treatment for mild bleeding episodes. DDAVP has been shown to be effective in many bleeding disorders, including inherited platelet function disorders. However, DDAVP efficacy among GT patients has not been established and guideline recommendations are conflicting.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002736", "CG-AC:RF002740", "CG-AC:RF000679", "CG-AC:RF002743" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACPM5222", "id": "CG-AC:AC1009/tr/ACPM5222", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Recombinant activated factor VII (rFVIIa) may be considered for patients with: moderate to severe acute bleeding; for treatment of refractory minor bleeds; for prophylaxis in patients with frequent severe bleeds; treatment during minor and major surgery; and in patients who are refractory to platelet transfusion. Some guidelines suggest utilizing rFVIIa as a first line therapy and saving platelet transfusion for more severe or non-responsive bleeds. High doses have been successful, particularly if used early and upfront. rFVIIa in a dose of =80 µg/kg at intervals of 2.5 h or less were observed to be safe and effective in nonsurgical bleeds, minor and major procedures in patients with or without antibodies, and/or refractoriness.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002736", "CG-AC:RF002740", "CG-AC:RF002743" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/tr/ACPM5221", "id": "CG-AC:AC1009/tr/ACPM5221", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Inherited platelet disorders are rare and require specialist management. All patients with such disorders should be registered with a hemophilia center with appropriate facilities for investigation, treatment and 24-h open access. Affected individuals should carry identification cards indicating the diagnosis, special instructions as needed such as platelets, immunization, and severity, and contact information for the treating physician or clinic.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002736", "CG-AC:RF002740" ] } ] }, "evidenceCategory": { "outcomeEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/oei", "id": "CG-AC:AC1009/oei", "type": "EvidenceItem", "natureOfTheThreat": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/oei/nott", "id": "CG-AC:AC1009/oei/nott", "type": "EvidenceLine", "prevalenceOfTheGeneticDisorder": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/oei/pgd", "id": "CG-AC:AC1009/oei/pgd", "type": "EvidenceItem", "keyText": "< 1-2 in 100000", "sourceOfPopulation": "General population", "evidenceNarrative": { "@id": "CG-AC:AC1009/en/potgd" } }, "clinicalFeatures": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/oei/cf", "id": "CG-AC:AC1009/oei/cf", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC1009/en/cf" } }, "naturalHistory": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/oei/nh", "id": "CG-AC:AC1009/oei/nh", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC1009/en/nh" } } }, "threatMaterializationChances": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/oei/tmc", "id": "CG-AC:AC1009/oei/tmc", "type": "EvidenceLine", "modeOfInheritance": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1009/oei/moi", "id": "CG-AC:AC1009/oei/moi", "type": "EvidenceItem", "keyText": "Autosomal Recessive", "evidenceNarrative": { "@id": "CG-AC:AC1009/en/ACMI2619" } }, "prevalenceOfTheGeneticMutation": { "@id": 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