Commonly Encountered Hematologic Chief Complaints in the Pediatric Pa8ent Black Hills Pediatric Symposium 6/23/17 Sam Milanovich, MD Pediatric
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1 Commonly Encountered Hematologic Chief Complaints in the Pediatric Pa8ent Black Hills Pediatric Symposium 6/23/17 Sam Milanovich, MD Pediatric Hematology/Oncology Sanford Children s Specialty Clinic Sioux Falls, SD
2 Type of Bleeding Clinical Characteris-c Primary Hemosta-c Defect Clo5ng Factor Deficiency Site of bleeding Skin, Mucous Membranes SoI Tissues, Muscles, Joints Bleeding aier minor cuts Yes Rare Petechiae Present Absent Ecchymosis Small, Superficial Large, Deep, Palpable Hemarthrosis Rare Common Bleeding aier trauma/surgery Immediate Delayed Nathan & Oski, 2015
3 Case 1 13 year old female presents with pallor, faxgue, lightheadedness. History is remarkable for menses 2 months earlier. Describes periods as inixally heavy Most recently very heavy.
4 Case 1: Menorrhagia History Other bleeding symptoms: quanxfy Nosebleeds, bruising HemostaXc challenges Surgeries, tonsillectomy/adenoidectomy, dental work Family History Women with gynecologic bleeding Peripartum transfusions, hysterectomies Other bleeding: surgeries
5 Case 1: Menorrhagia DifferenXal Diagnoses Congenital Von Willebrand Disease Platelet funcxon defect Glanzman Thrombasthenia, Storage-Pool Defect, etc Thrombocytopenia Wiskod Aldrich, Bernard-Soulier, etc Acquired Thrombocytopenia ITP, AplasXc Anemia, Leukemia Coagulopathy Liver disease, von Willebrand Disease
6 Case 1: Menorrhagia Lab Tests CBC w/ manual differenxal Von Willebrand Factor AcXvity (aka ristocexn cofactor acxvity) Von Willebrand Factor AnXgen Factor VIII acxvity If above are non diagnosxc Platelet aggregaxon studies Note about PFA-1000 Quick screen, mainly detects Von Willebrand AcXvity and more severe hemostaxc defects
7 Case 1: Menorrhagia Management Whether a bleeding disorder is idenxfied or not, management may be similar Hormonal suppression Combined oral contracepxve, oien Xmes need higher dose, 3-4 tabs/day and taper down. IV estrogen in severe cases Consider consultaxon with gynecologist if needing high doses of estrogen IUD, depo shots, etc AnXfibrinolyXc Tranexamic Acid (Lysteda): 1300 mg PO TID x 5 days
8 Case 1: Menorrhagia Management DDAVP Some type 1 VWD and some platelet funcxon defects may respond to DDAVP (intranasal aka SXmate, or IV for procedures/emergencies) Dose is higher than for enuresis Need to limit free water to maintenance intake for 24 hours DDAVP challenge tesxng recommended Baseline VWF acxvity/platelet agg, 1 and 4 hours post-ddavp dose.
9 Case 1: Menorrhagia Caveats Estrogen may increase Factor VIII and von Willebrand factor levels = draw studies before starxng hormonal therapy. They are also elevated in response to stress and may need to be repeated. Hormonal contracepxves (Estrogen > Progesterone) and Lysteda are associated with increased risk of thromboembolism. Especially with other risk factors: smoking, age >35, obesity, immobility
10 Case 2 12 yo female requiring orthopedic surgery for hip. Family asking about risk of blood clots Detailed Family History DVTs PE MI or stroke (at young age) Miscarriages
11 Case 2: Inherited Thrombophilia DifferenXal Factor V Leiden Prothrombin Gene MutaXon AnXthrombin III deficiency Elevated Factor VIII Hyperhomocysteinemia Associated with MTHFR mutaxons Acquired AnXcardiolipin anxbody Syndrome: lupus anxcoagulant etc Pregnancy, smoking, estrogen
12 Case 2: Inherited Thrombophilia Management If family history: consider prophylaxis in situaxons of increased risk: Major orthopedic surgery Extended travel Prolonged immobility Avoid risk factors: smoking, pregnancy, etc If paxent develops clot + heritable factor idenxfied AnXcoagulaXon 6-12 months vs life-long Depending on severity/circumstances of clot, may warrant trial off anxcoagulaxon. If recurrent clot, likely life long anxcoagulaxon
13 Case 3 6 yo male with history of obstrucxve sleep apnea. Seen by ENT and recommend tonsillectomy and adenoidectomy. The otolaryngologist asks pediatrician for pre-op assessment. Do you order PT/PTT, CBC?
14 Case 3: abnormal coag labs Detailed medical history and family history are important. If there is no history of bleeding in paxent: epistaxis, bruising, hematochezia, prior surgeries AND There is no family history of bleeding complicaxons, nosebleeds, menorrhagia, etc. PT/PTT is unlikely to uncover a clinically significant bleeding disorder More common disorder that may cause complicaxon such as VWD or platelet funcxon defect are unlikely to be detected by PT/PTT
15 Case 3: abnormal coag labs PT and PTT are obtained and PTT is prolonged, now what? 1:1 mixing study: to determine deficiency vs an inhibitor Aka an anxbody against a coagulaxon cascade factor. Mix 1 part paxent plasma with 1 part normal plasma that has normal factor levels. If it corrects = PTT returns to normal = deficiency of a factor If it remains prolonged = inhibitor presence = interfering with laboratory assay, may or may not be clinically relevant. If procedure is elecxve reschedule and wait for return to normal Correlate with history If procedure urgently indicated.
16 Case 3: abnormal coag labs Management Replacement of deficient factor (if clinically relevant) Factor XII deficiency: common, clinically insignificant but prolongs PTT
17 Case 4 15 yo female presents with easy bruising, oien no trauma, several hematomas. History reveals heavy periods and gingival bleeding with brushing teeth. Exam: tall and thin, joint laxity DifferenXal: Von Willebrand Disease, Platelet FuncXon Defect, ConnecXve Xssue disorder
18 Case 4: Connec8ve Tissue Disease Ehlers-Danlos Osteogenesis Imperfecta Marfan Syndrome Loeys-Dietz Syndrome Diagnosis Thorough exam and history Platelet aggs, CBC, VWF studies normal.
19 Case 4: Connec8ve Tissue Disease Management Avoidance of factors that cause vascular disease: smoking, hypertension, etc Ascorbic Acid: co-factor for collagen cross-linking, may reduce bruising. Avoid NSAIDs and vascular procedures/manipulaxons. DDAVP may be beneficially around dental procedures, minor procedures Factor VIIa for serious bleeding, consider for major surgery
20 Nathan & Oski, 2015
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