Platelet disorders Notes

NOTES NOTES PLATELET DISORDERS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Platelet dysfunction, impaired hemostasis, bleeding RISK FACTORS DIAGNOSIS LAB RESULTS ▪ Complete blood count (CBC) ▪ Clotting studies (e.g. bleeding time) ▪ Platelet function tests ▪ Children of parents who are close relatives (consanguineous) COMPLICATIONS ▪ Mild to severe hemorrhage SIGNS & SYMPTOMS ▪ Mucocutaneous bleeding ▪ Excessive bruising/bleeding after minor trauma ▪ Immediate, excessive bleeding with invasive procedures TREATMENT ▪ Manage spontaneous/trauma-related bleeding episodes MEDICATIONS ▪ ▪ ▪ ▪ Anti-fibrinolytic therapy Platelet transfusions Avoid antiplatelet medications Corticosteroids, immunosuppressants BERNARD–SOULIER SYNDROME (BSS) osms.it/bernard-soulier-syndrome PATHOLOGY & CAUSES ▪ Rare, inherited clotting disorder; mild thrombocytopenia, macrothrombocytopenia (giant platelets), platelet dysfunction, bleeding CAUSES ▪ Autosomal recessive inheritance pattern 444 OSMOSIS.ORG ▪ Platelets lack essential glycoprotein Ib-IX-V complex (GPIb) → impaired hemostasis → bleeding RISK FACTORS ▪ Prevalence in individuals of Mediterranean descent ▪ Children of parents who are close relatives (consanguineous)

Chapter 56 Platelet Disorders SIGNS & SYMPTOMS ▪ Mucocutaneous bleeding ▫ Epistaxis; gingival bleeding; petechiae, purpura (coalesced petechiae); GI bleeding; genitourinary bleeding (e.g. hematuria); menorrhagia ▪ Excessive bruising/bleeding after minor trauma; bruises linger ▪ Immediate, excessive bleeding with invasive procedures ▪ Asymptomatic until adulthood DIAGNOSIS LAB RESULTS ▪ CBC ▫ Low platelet count ▪ Peripheral blood smear analysis ▫ Giant platelets (accelerated platelet turnover) ▪ Clotting studies ▫ Bleeding time prolonged (PT, aPTT normal) ▪ Flow cytometry ▫ Deficient/absent GPIb-IX-V complex OTHER DIAGNOSTICS ▪ Physical examination ▫ Purpura ▫ Ecchymoses TREATMENT MEDICATIONS ▪ Avoid antiplatelet medications ▪ Anti-fibrinolytic therapy (e.g. tranexamic acid) OTHER INTERVENTIONS ▪ Platelet transfusions (e.g. prophylaxis before invasive procedures) ▫ HLA matching/leukocyte reduced platelets reduces risk of allo-antibody formation GLANZMANN'S THROMBASTHENIA (GT) osms.it/glanzmanns-thrombasthenia PATHOLOGY & CAUSES ▪ Inherited bleeding disorder, defect in platelet surface receptor αIIbβ3 ▪ Platelet-mediated hemostasis ▫ Binding of platelets to exposed components of injured endothelium through glycoprotein (GP) receptors on platelet surface (e.g. GPIb/IX, GPIa/IIa, integrin αIIbβ3) ▪ Integrin αIIbβ3 defect → impaired platelet clot retraction, altered hemostasis CAUSES ▪ Autosomal recessive inheritance pattern ▪ Rarely, allo-/auto-antibodies to platelet αIIbβ3 produced by autoimmune conditions (e.g. systemic lupus erythematosus, immune thrombocytopenia, myelodysplastic syndrome) during pregnancy/with use of platelet integrin αIIbβ3 antagonists (abciximab, eptifibatide) RISK FACTORS ▪ Slightly more common in individuals who are biologically female ▪ Children of parents who are close relatives OSMOSIS.ORG 445

▪ Conditions requiring frequent platelet transfusion ▫ Platelet alloimmunization COMPLICATIONS ▪ Fatal bleeding ▫ Risk increases during childbirth (maternofetal bleeding, primary/ secondary postpartum hemorrhage) SIGNS & SYMPTOMS ▪ Mucocutaneous bleeding ▫ Epistaxis; gingival bleeding; petechiae, purpura (coalesced petechiae); gastrointestinal (GI) bleeding; genitourinary bleeding (e.g. hematuria); menorrhagia ▪ Excessive bruising/bleeding after minor trauma ▪ Immediate, excessive bleeding with invasive procedures ▪ Infants ▫ Leukocytosis, delayed separation of umbilical cord, purpura, spontaneous bruising, mucocutaneous bleeding DIAGNOSIS LAB RESULTS ▪ CBC ▫ Platelet count normal ▪ Clotting studies ▫ Bleeding time prolonged (PT, aPTT normal) ▪ Light transmission aggregometry (LTA) ▫ Determines degree of platelet aggregation ▫ Decreased or absent in GT ▪ Platelet function analyzer (PFA) ▫ Measures flow rate as platelets form platelet plug within capillary tube ▫ Formation of platelet plug prolonged in GT 446 OSMOSIS.ORG ▪ Flow cytometry ▫ Deficient/absent αIIbβ3 platelet receptors ▫ Mutation analysis through genomic DNA sequencing OTHER DIAGNOSTICS ▪ Physical examination ▫ Purpura ▫ Ecchymoses TREATMENT ▪ Avoid antiplatelet medications, punctures, invasive procedures MEDICATIONS ▪ Individuals who are biologically female, of childbearing age ▫ Metrorrhagia: oral contraceptives (suppress menstrual periods); iron supplementation; hysterectomy (if bleeding severe) ▫ Childbirth: prophylaxis with recombinant factor VIIa + antifibrinolytic agent ▪ Rituximab, corticosteroids, immunosuppressants (e.g. cyclophosphamide) OTHER INTERVENTIONS ▪ Manage bleeding episodes ▫ Compression, fibrin sealants, gelatin sponges, nasal packing, topical thrombin, anti-fibrinolytic therapy (e.g. tranexamic acid), recombinant factor VIIa ▪ Platelet transfusions (e.g. prophylaxis before invasive procedures) ▫ HLA matching/administration of leukocyte reduced platelets reduces allo-antibody formation ▪ Oral hygiene mitigates gingival bleeding ▪ Hematopoietic cell transplantation (if bleeding severe, recurrent)