HEMOPHILIA AND VON WILLEBRAND DISEASE EMERGENCIES

Transcription

1 HEMOPHILIA AND VON WILLEBRAND DISEASE EMERGENCIES ALGORITHM. Hemphilia and vn Willebrand Disease Factr Replacement Therapy! Gal fr factr replacement is 30 minutes r less fr suspected head bleeds and 60 minutes r less fr suspected bleeding in areas ther than the head Patient presents t ED Inclusin Criteria: Diagnsis f Hemphilia Exclusin Criteria: Patients with Planned Admissin! If patient is n emicizumab-kxwh please see prblem list and cnsult hematlgy Indicatins fr Factr Replacement Therapy Suspected bleeding int a jint r muscle Any significant injury t the head, neck, muth r eyes, r evidence f bleeding in thse areas Any new r unusual headache, particularly ne fllwing trauma Severe pain r swelling at any site All pen wunds requiring surgical clsure, wund adhesive, r Steri-Strips Histry f an accident r trauma that might result in internal bleeding Any invasive prcedure r surgery Heavy r persistent bleeding frm any site Gastrintestinal bleeding Acute fractures, dislcatins and sprains Is factr replacement indicted? (see indicatins t the left) Yes Check patient s prblem list fr bleed plan dcumented under Hemphilia Diagnsis r vn Willebrand disease NO Off Pathway. Cntinue care as clinically indicated Pharmacist t verify factr. If pharmacist is nt available, nurse t verify at bedside. Allw patient/caregiver t recnstitute and administer wn prduct. YES Did patient bring cltting factr? NO What des the patient use at hme? If nt knwn, review EHR, see table belw fr substitutins, and/r cnsult hematlgist. Pearls: P1: When in dubt, administer cltting factr replacement therapy P2: Cltting factr replacement therapy shuld be infused prir t any labs, radilgic studies, r prcedures P3: Ntify n-call hematlgist immediately Initiate factr replacement therapy with preferred prduct YES Is preferred prduct available in pharmacy? P4: Patient r caregiver s suspicin f bleeding-related prblem is sufficient t initiate factr replacement therapy P5: Only rder diagnstic tests if they will change the utcme P6: Allw patient t use wn prduct NO P7: Patients with factr IX deficiency are at risk fr anaphylaxis P8: Rund dse up t the nearest vial size and give the entire vial (d nt thrw away extra factr) unless Hemphilia A patient weighing less tan 5 kg r Hemphilia B patients weighing less than 2 kg Alert CHCO inpatient pharmacy t rder patients preferred prduct frm HTC ( ) if patient is admitted Mnday-Friday 8am-5pm, factr available within tw hurs All ther hurs, factr available within 4 hurs Initiate factr replacement therapy with substitute CHCO frmulary prduct belw (see Table 1 fr apprpriate substitute): If patient needs factr VIII use Advate If patient needs factr IX use BeneFIX If patient needs factr VIII use w/vwf Humate-P If patient needs FEIBA If patient needs rfviia If patient needs dse f DDAVP Page 1 f 13

2 TABLE OF CONTENTS Algrithm Target Ppulatin Clinical Management Clinical Assessment Labratry and Radilgy Studies Therapeutics Admissin Criteria Discharge Criteria Fllw-Up Table 1 Prduct Replacement Guide Table 2 Desmpressin (DDVAP = CHCO frmulary) Dsing Table 3 Anti-Fibrinlytics References Clinical Imprvement Team TARGET POPULATION Inclusin Criteria Patients with a diagnsis f hemphilia r vn Willebrand disease and histry f injury, cmplaint f pain, r ther cncern fr bleeding Exclusin Criteria Patients with planned admissin CLINICAL MANAGEMENT Initial Triage Triage shuld be urgent. Delays in administering factr cncentrate treatment significantly affect mrbidity and mrtality in individuals with hemphilia r vn Willebrand disease 1 The six majr sites fr serius bleeding which threaten life, limb, r functin are 2 : Intracranial Spinal crd Thrat/muth Intra-abdminal Limb cmpartments Ocular All f the abve require immediate assessment and interventin, and are characterized by 2 Page 2 f 13

3 Bleeding int an enclsed space Cmpressin f vital tissues Ptential lss f life, limb, r functin CLINICAL ASSESSMENT Treatment fr a suspected bleeding episde is based n clinical histry. Many physical exam findings tend t be nrmal in the early phases f mst hemphilic bleeds. Spntaneus bleeding is cmmn in individuals with severe disease. When in dubt, administer cltting factr replacement therapy 1 Treatment decisins shuld be based n the suspicin f a bleeding-related prblem, nt a cnfirmed diagnsis f ne 1 If, in their experience, the patient r caregiver suspects ccult bleeding is ccurring, administer cltting factr replacement. Patients ften are instructed in and/r carry with them apprpriate factr replacement dsing guidelines as advised by their treating hematlgist 1 Cnsultatin with the patient's hematlgist r a reginal hemphilia treatment center prfessinal is strngly advised; hwever, this shuld nt delay administratin f cltting factr 1 Signs and symptms 2 : Head: Early neurlgical symptms may nt be evident due t the slw, zing nature f hemphilia bleeding Headache with increasing severity Irritability Vmiting Seizures Visin prblems Fcal neurlgical deficits Stiff neck Altered mental status r change in level f cnsciusness Jint bleeding: Pain Restricted mvement Swelling Warmth Erythema n and arund the jint Patient may reprt symptms f bubbling r tingling sensatin with n physical signs Later symptms may include: A feeling f fullness within the jint Mderate t severe pain Muscle/Sft Tissue bleeding: Any muscle grup may be subject t bleeding. Cmmn bleeding sites include upper arm, frearm, thigh, calf muscles, abdminal wall muscles, and ilipsas muscles Page 3 f 13

4 Abdminal muscles generally d nt have bservable swelling, but may have a palpable mass, rigidity, and pain Lwer abdminal r grin pain, especially with signs f nerve cmpressin may indicate an iliapsas bleed Other muscles may exhibit: Warmth Pain Swelling Sft tissue bleeds usually d nt require aggressive treatment. Superficial hematmas and bruises may appear anywhere n the bdy and, if they d nt threaten functin and mbility, they d nt need t be treated Gastrintestinal/Urinary Tract bleeding: Abdminal pain Flank pain Hematuria Melena Vmiting bld Drpping hemglbin Steady drpping hemglbin may indicate bleed in abdminal cavity Dramatic drp in hemglbin fllwing trauma may indicate rupture f liver, spleen, r pancreas Mucus Membrane/Oral bleeding: Pain Swelling Difficulty swallwing Difficulty breathing Vmiting triggered by swallwed bld Patient may reprt the sensatin f pstnasal drip (bld running dwn back f thrat frm psterir epistaxis) r may reprt tasting bld LABORATORY STUDIES IMAGING Diagnstic tests are nly indicated if they will change utcme Cltting factr replacement therapy shuld be given befre any diagnstic studies (radigraphs, CT scans etc.) are perfrmed in the evaluatin f a suspected bleeding prblem, especially in the case f head trauma r suspected intracranial hemrrhage. Fr rutine jint bleeding, n radigraphic studies are indicated 1 If invasive prcedure (lumbar puncture, arterial bld gas, arthrcentesis, etc.) r surgery is necessary, factr replacement therapy must be administered in the emergency department befrehand 1. Factr will be distributed and circulating 15 minutes pst IV push Fr an individual with knwn hemphilia, rutine labratry studies (PT, PTT, factr levels), are nt indicated in the treatment f a rutine bleeding episde unless requested by the patient s hematlgist. The clinical severity f a patient's hemphilia is gauged by his r her baseline cltting factr level, a value that remains fairly cnstant thrughut that persn's life 1 Page 4 f 13

5 THERAPEUTICS (SEE TABLES 1, 2, AND 3 FOR DOSING) Refer t bleed treatment plan dcumented in patient s Prblem List under hemphilia diagnsis. A unique plan will be dcumented in the Prblem List fr all knwn hemphilia patients seen by CHCO hematlgy Mst bleeds will require factr replacement except fr bruises and minr sft tissue injuries that d nt impact functin and mbility Treatment fr bleeding invlves replacing the deficient factr as the first curse f actin. This requires intravenus infusin f factr cncentrates. Specific dses, additinal drugs, and medical interventins depend upn the site and severity f bleeding. Once factr replacement therapy has been infused, diagnstic prcedures and examinatins can begin Gal time (frm presentatin t ER) fr start f administratin f factr replacement is 30 minutes r less fr suspected head bleeds and 60 minutes r less fr suspected bleeding in areas ther than the head Indicatins fr factr replacement therapy 1 : Suspected bleeding int a jint r muscle Any significant injury t the head, neck, muth r eyes, r evidence f bleeding in thse areas Any new r unusual headache, particularly ne fllwing trauma Severe pain r swelling at any site All pen wunds requiring surgical clsure, wund adhesive, r Steri-Strips Histry f an accident r trauma that might result in internal bleeding Any invasive prcedure r surgery Heavy r persistent bleeding frm any site Gastrintestinal bleeding Acute fractures, dislcatins and sprains Cnsideratins fr factr replacement therapy: If a patient with hemphilia r the parent f a patient with hemphilia brings cltting factr with them t the emergency department, allw them t use it. The identity and integrity f a patient s wn medicatin shuld be verified and dcumented by a Children s Hspital Clrad pharmacist prir t administratin. In the event a pharmacist is nt available t cnduct this review prmptly, the patient s wn medicatin may be checked by the nurse caring fr the patient. The patient r caregiver shuld be permitted t recnstitute the prduct and administer it whenever pssible. Individuals with bleeding disrders are encuraged t have an emergency dse f factr cncentrate r DDAVP in their hme and t take it with them when they travel. In thse situatins where a patient des nt bring their wn cltting factr cncentrate, emergency departments must be prepared t prvide cltting factr replacement. Emergency departments must have ready access t factr replacement prducts s that they are available within ne hur f the patient's arrival 1 Factr replacement must be administered intravenusly by IV push ver 1 t 2 minutes 1 Dse factr up t the "clsest vial" by size/assay and infuse the full cntent f each recnstituted vial. A mderate excess f factr cncentrate will nt create a hypercaguable state but will prlng the therapeutic level f the prduct administered; thus it is prudent t rund up 1 Fr individuals with inhibitrs (antibdies t factr VIII r IX), treatment decisins may be mre cmplicated. Cnsult hematlgy When treating an individual with mild hemphilia A wh is respnsive t desmpressin (CHCO frmulary = DDAVP), the dse and prir respnsiveness are usually knwn Page 5 f 13

6 The mst experienced IV therapist r phlebtmist shuld perfrm any venipuncture. Traumatic venipunctures and repeated needle sticks cause painful hematmas that may limit further IV access and lead t cmpartment syndrme 1 Factr infusin kits usually include butterfly needles, which are preferred. If IV access is necessary in therwise hemdynamically stable patients, the smallest pssible gauge needle shuld be utilized (25g butterfly needles in yung infants, 23g butterfly needles in lder children and adults) 1 In any suspected bleeding emergency in which the cltting factr level f an individual with hemphilia is unknwn, the factr level shuld be assumed t be 0% 1 Intramuscular injectins shuld be avided whenever pssible. If they must be given, factr replacement therapy shuld precede the injectin. Parenteral agents shuld be given intravenusly r subcutaneusly. Tetanus immunizatins may be administered subcutaneusly 1 Turniquets shuld nt be applied tightly t extremities because they may cause bleeding 1 Analgesics and Antipyretics: Aspirin and aspirin-cntaining prducts are cntraindicated in individuals with hemphilia Acetaminphen and/r ther pain medicatins (such as mrphine r hydrcdne) may be used fr analgesia Nn-steridal anti-inflammatry drugs may be carefully administered t select patients, such as individuals with chrnic arthritic pain wh are nt actively bleeding r being treated fr a recent bleeding prblem 1 If an individual with hemphilia is bleeding and requires transprtatin t anther facility fr definitive care, all effrts shuld be made t replace the deficient cltting factr befre transprt 1 Hemphilia A withut Inhibitr The treatment f chice fr individuals with hemphilia A (factr VIII deficiency) is recmbinant factr VIII r the patient s prduct f chice. Plasma-derived cncentrate is a suitable alternative in an emergency situatin when recmbinant Factr VIII is nt available. See: Hemphilia and vn Willebrand Disease Factr Replacement Therapy Algrithm When bleeding is severe, the apprpriate dse f factr VIII is 50 units/kg. If patient weighs less than 5 kg d nt exceed 75 units/kg crrectin when runding t vial size (in a patient less than 5 kg yu may NOT be able t use the entire vial) Cryprecipate and fresh frzen plasma are n lnger recmmended fr treatment f individuals with hemphilia A 1 Mild Hemphilia A with Nn-Life r Limb Threatening Bleeding Individuals with mild hemphilia A (factr VIII greater than 5%) wh are experiencing nn-life r limb threatening bleeding may respnd t desmpressin (CHCO frmulary = DDAVP) if they have been shwn t respnd t this treatment previusly. Otherwise, treatment is the same as fr ther individuals with hemphilia A1 Desmpressin (CHCO frmulary = DDAVP)1: 0.3mcg/kg subcutaneusly r Desmpressin (CHCO frmulary = DDAVP)1: 0.3mcg/kg diluted in 30 ml nrmal saline infused ver 30 minutes r Intranasally via ultra-cncentrated nasal spray "Stimate": Fr patients less than 50 kg: 1 spray in ne nstril Fr patients greater 50 kg: 1 spray in each nstril Page 6 f 13

7 Hemphilia B withut Inhibitr The treatment f chice fr individuals with hemphilia B (factr IX deficiency) is recmbinant factr IX r the patient s prduct they usually receive at hme. Plasma-derived cncentrate, see list f factr IX prducts in Table 1, is a suitable alternative in an emergency situatin when recmbinant Factr IX is nt available. See: Hemphilia and vn Willebrand Disease Factr Replacement Therapy Severe factr IX deficient patients are at risk f anaphylaxis and nephrtic syndrme Factr IX recvery is unpredictable (ften lwer recvery) when using BeneFIX If patient treated with BeneFIX cntinues t bleed, check a STAT Factr IX activity and redse When bleeding is severe, the apprpriate dse f factr IX is 120 units/kg If patient weighs less than 2 kg d nt exceed 150 units/kg crrectin when runding t vial size (in a patient less than 2 kg yu may NOT be able t use the entire vial) Fresh frzen plasma is n lnger recmmended fr treatment f individuals with hemphilia B. Nte that cryprecipitate des nt cntain Factr IX 1 Hemphilia with Inhibitr The care f inhibitr patients shuld be urgently discussed with the patient's hematlgist. If an individual with an inhibitr presents in a life- r limb-threatening scenari, the safest immediate actin is t prescribe recmbinant factr VIIa (rfviia) at a dse f 90 mcg/kg r higher (see patients plan in prblem list) activated prthrmbin cmplex cncentrates (FEIBA) at 75 units/kg. The patient r family can als prvide infrmatin n respnse t therapeutic bypassing agents1 Patients taking Emicizumab-kxwh shuld nt get FEIBA. Please see patient prblem list Nte: In factr IX patients with a histry f inhibitrs and anaphylaxis d nt give factr IX-cntaining prducts (FEIBA) unless the bleeding is life-threatening1 Anti-fibrinlytics Anti-fibrinlytics are cntraindicated in patients with hematuria Amincapric Acid: Can be given PO r IV if needed Lading dse: 50 t 200 mg/kg PO r IV every 6 hurs fr 3 t 10 days. Dse nt t exceed 4 grams Maintenance dse: mg/kg/dse PO r IV every 6 hurs Tranexamic Acid (TXA): 1300 mg rally every 8 hurs fr 5 days10 mg/kg/dse IV every 6 hurs r 10 mg/kg/dse IV nce t lad then 10/mg/kg/hur IV cntinuus infusin (maximum 1000 mg/dse) Other Mdalities 2 (Evidence quality: D) 1. Prtect (bracing) 2. Rest 3. Ice packs 4. Cmpressin (Ace wrap) 5. Elevatin Page 7 f 13

8 ADMISSION CRITERIA Discuss admissin with hematlgist DISCHARGE CRITERIA Discuss discharge plan with hematlgist. If patient is t be discharged, determine whether r nt t leave the prt accessed r PIV in place and prvided necessary teaching t caregivers FOLLOW-UP Ntify patient s hematlgist r Hemphilia and Thrmbsis Center Table 1. Prduct Replacement Guide Prduct type Factr VIII Recmbinant Factr VIII plasma derived with vwf Prduct Name (Brand) Advate Adynvate Afstyla Elctate Helixate FS Kgenate FS Kvaltry Nveight Nuwiq Obizur Recmbinate Xyntha Xyntha Slfuse Alphanate (fr hemphilia A) Wilate (fr hemphilia A) CHCO Stck Prduct Advate Advate Dse fr Majr Acute Bleed (Range) 50 units/kg (30-50 units/kg) 50 units/kg (30-50 units/kg) Cmments 1 unit f any ther brand f Factr VIII is equal t 1 unit f Advate fr maintenance dsing 1 unit f any ther brand f Factr VIII is equal t 1 unit f Advate fr maintenance dsing Factr IX Recmbinant Factr IX plasma derived Alprlix BeneFIX Idelvin Ixinity Rebinyn Rixubis AlphaNine SD Mnnine BeneFIX BeneFIX 120 units/kg ( units/kg) 120 units/kg ( units/kg) 1 unit f any ther brand f Factr IX is equal t 1.2 units f BeneFix fr maintenance dsing 1 unit f any ther brand f Factr IX is equal t 1.2 units f BeneFix fr maintenance dsing Page 8 f 13

9 Factr VIII with vwf Cmplex Alphanate (fr VWF disease) Humate-P Wilate Humate-P 60 VWF:RC units/kg (20-80 units/kg) Vnvendi Factr VIIa Recmbinant Anti-inhibitr Cagulant Cmplex NvSeven RT FEIBA NF NvSeven RT FEIBA NF 90mcg/kg (30-270mcg/kg) 75 units/kg (50-85 units/kg) *Refer t Black bx warning belw *Black Bx Warning FEIBA NF: Thrmbtic and thrmbemblic events have been reprted during pst-marketing surveillance fllwing infusin f FEIBA VH r FEIBA NF, particularly fllwing the administratin f high dses and/r in patients with thrmbtic risk factrs Refer t patient s Snapsht in Epic fr hemrrhage plan. If available, patient s hemrrhage plan supersedes dse in this chart Emicizumab-kxwh is the first in a new class f drugs nly fr peple with hemphilia A. It is a nvel bi-specific antibdy that bypasses FVIII and allws hemphilia A patient with and withut inhibitrs have high quality prphylaxis. It is nt fr treating acute bleeding. The phase 3 clinical trial in adults and children with inhibitrs shwed efficacy, and its use in nn-inhibitr patients is pending FDA apprval sn. Cmplicatins ccurred during the trial, all when trying t treat bleeding. They were thrmbsis and thrmbtic micrangipathy all assciated with the imprper use f FEIBA. Because f this FEIBA is cntraindicated and t treat bleeding the PI dse f rfviia is recmmended: 90 mcg/kg/dse. Increasing numbers f patients are starting emicizumab-kxwh. Instructins fr treating bleeding are in the Prblem List and the Hematlgist n call shuld be ntified when treating a patient n emicizumab-kxwh Table 2. Desmpressin (DDVAP = CHCO frmulary) Dsing Rute Subcutaneusly Dse 0.3mcg/kg subcutaneusly Intravenusly Intranasally via ultra-cncentrated nasal spray "Stimate" 0.3mcg/kg diluted in 30 ml nrmal saline infused ver 30 minutes Fr patients less than 50 kg: 1 spray in ne nstril Fr patients greater 50 kg: 1 spray in each nstril Page 9 f 13

10 Table 3. Anti-fibrinlytics Nte: Anti-fibrinlytics are cntraindicated in patients with hematuria Prduct Amincapric Acid: Can be given rally r IV if needed Tranexamic Acid (TXA) Dsing Lading dse: 50 t 200 mg/kg rally r IV every 6 hurs fr 3 t 10 days. Dse nt t exceed 4 grams Maintenance dse: mg/kg/dse rally r IV every 6 hurs Oral: 1300 mg rally every 8 hurs fr 5 days IV: 10 mg/kg/dse IV every 6 hurs r 10 mg/kg/dse IV nce t lad then 10/mg/kg/hur IV cntinuus infusin Page 10 f 13

11 REFERENCES 1. Natinal Hemphilia Fundatin. Guidelines fr Emergency Department Management f Individuals with Hemphilia Emergency Care fr Patients with Hemphilia. Third ed: Clarence Printing; American Academy f Pediatrics. Classifying recmmendatins fr clinical practice guidelines. Pediatrics 2004;114: Natinal Heart, Lung, and Bld Institute (NHLBI). The Diagnsis, Evaluatin and Management f vn Willebrand Disease Natinal Heart, Lung, and Bld Institute (NHLBI). Vn Willebrand disease (VWD): evidence-based diagnsis and management guidelineshaemphilia: The Official Jurnal Of The Wrld Federatin Of Hemphilia, 14(2), di: /j x Page 11 f 13

12 CLINICAL IMPROVEMENT TEAM MEMBERS Michael Wang, MD Pediatric Hematlgist Timthy Schardt, Pharm D, BCPS Clinical Pharmacist fr Investigatinal Drug Services and Anticagulatin Julia Freeman, MD Pediatric Emergency Medicine Jni MacKenzie, MS, CPNP Emergency Clinical Practice Specialist Claire Zafirpuls Clinical Effectiveness Paige Krack Clinical Effectiveness APPROVED BY Clinical Pathways and Measures Cmmittee - May 9, 2018 Pharmacy and Therapeutics Cmmittee - May 3, 2018 MANUAL/DEPARTMENT Clinical Pathways/Quality ORIGINATION DATE January 3, 2014 LAST DATE OF REVIEW OR REVISION May 9, 2018 APPROVED BY Lalit Bajaj, MD, MPH Medical Directr, Clinical Effectiveness REVIEW/REVISION SCHEDULE Scheduled fr full review n May 9, 2022 Clinical pathways are intended fr infrmatinal purpses nly. They are current at the date f publicatin and are reviewed n a regular basis t align with the best available evidence. Sme infrmatin and links may nt be available t external viewers. External viewers are encuraged t cnsult ther available surces if needed t cnfirm and supplement the cntent presented in the clinical pathways. Clinical pathways are nt intended t take the place f a physician s r ther health care prvider s advice, and is nt intended t diagnse, treat, cure r prevent any disease r ther medical cnditin. The infrmatin shuld nt be used in place f a visit, call, cnsultatin r advice f a physician r ther health care prvider. Furthermre, the infrmatin is prvided fr use slely at yur wn risk. CHCO accepts n liability fr the cntent, r fr the cnsequences f any actins taken n the basis f the infrmatin prvided. The infrmatin prvided t yu and the actins taken theref are prvided n an as is basis withut any warranty f any kind, express r implied, frm CHCO. CHCO declares n affiliatin, spnsrship, nr any partnerships with any listed rganizatin, r its respective directrs, fficers, emplyees, agents, cntractrs, affiliates, and representatives. Page 12 f 13

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