Management of acute bleeding & emergency in hemophilia

Novie Amelia Chozie, Fitri Primacakti, Djajadiman Gatot

Divisi Hematologi-Onkologi

Departemen Ilmu Kesehatan Anak FKUI/RSCM Jakarta

Perdarahan akut, kapan mulai terjadi ?

•Bayi/anak laki-laki

•Lebam atau memar saat bayi

mulai belajar merangkak

•Usia 1 – 2 tahun :

•Paling sering : sendi & otot

•Spontan atau karena trauma

ringan

Perdarahan akut, kapan mulai terjadi ?

•Perdarahan lain :

•perdarahan frenulum (pada bayi)

•Lebam kebiruan di kulit

•Perdarahan otak

•Perdarahan saluran kemih

•Mimisan

•Pada hemofilia ringan : perdarahan pascatrauma/kecelakaan/tindakan medik (cabut gigi, khitan)

Guidelines for the Management of Hemophilia, WFH 2012

Sites of bleeding

Guidelines for the Management of Hemophilia, WFH 2012

Perdarahan sendi (hemartrosis) akut

•Pertolongan pertama : RICE

•Faktor konsentrat sesegera mungkin

(< 2 jam)

•Analgetik : parasetamol, COX-2 inhibitor

•Fisioterapi segera setelah sakit dan bengkak hilang

Hoots WK. Emergency care issues in hemophilia. WFH, 2007

WFH Guidelines 2013Acute bleeds should be treated as quickly as possible, preferably within 2 (two) hours.

If in doubt, treat.

Fig. The cycle initiated by hemarthrosis, leading to

chronic synovitis and progressive arthropathy.

J Am Acad Orthop Surg. 2004;12:234-245. Pharmacological Research 2017;115:192–199

Hemarthrosis & hemophilic arthropathy

Synovitis

The goal of treatment is to deactivate the synovium as quickly as possible and preserve joint function.

• Factor concentrate replacement : short treatment courses (6-8 weeks) of secondary prophylaxis with intensive physiotherapy

• Daily exercise to improve muscle strength and maintain joint motion

• Antiinflamation : NSAIDs (COX-2 inhibitors)

• Functional bracing

• Synovectomy

Haemophilia. 2013:19; e1–47.

Chronic haemophilic arthropathy

The goals of treatment :

• To improve joint function

• Relieve pain

• Assist patient to continue/resume normal activities of daily living.

Haemophilia. 2013:19; e1–47.

On-demand treatment

• Treatment after bleeding has occurred

• The past standard of care in many developed countries

• Outcome : long term arthropathy• Poor quality of life

• Potential increase cost of healthcare (joint surgery, etc)

World Federation of Hemophilia

Prophylaxis

• Prophylaxis is the treatment by intravenous injection of factor concentrate to prevent anticipated bleeding.

• Ahlberg, 19651

• Moderate hemophilia (F VIII/IX 15%) vs Severe hemophilia (<1%)• Less joint bleed

• Less musculoskeletal complication (i.e. arthropathy)

• Better quality of life

• Nilsson, 19922

• Hypothesis : converting patient with severe hemophilia to moderate hemophilia will decrease musculoskeletal complication

Acta Orthop Scand. 1965:77;3-132

J Intern Med. 1992:232:25-32

Low dose prophylaxis study, RSCM

OutcomeProphylaxis

n = 22

On-demand

n = 18p CI# 95%

Total bleeding episodes 10,4 ± 6,4 17,3 ± 8,8 0,006* 2,08–11,87

Joint bleeding episodes 5 ± 4,3 8

(3–30)

0,009^ 0,9–6,99

*non paired T-test ^ Mann-Whitney #CI = confidence interval

• Prospective, randomized study

• Low dose prophylaxis (10 IU/kg 2x/week) versus On-demand

• Mean age in prophylaxis group was 12 ± 3.5 years and median age in on-demand group was 11.9 (6.518.2) years.

• No inhibitor F VIII found in both groups

Dose calculation :

F VIII (unit):

BW (kg) x % (plasma target –patient F VIII ) x 0,5

F IX (unit):

BW (kg) x % (plasma target –patient F IX )

Replacement therapy

Bleeding

Hemofilia A Hemofilia B

Plasma Target (%) Duration (day) Plasma Target (%) Duration (day)

Joint 10-20 1-2* 10-20 1-2*

Muscle (excl.iliopsoas) 10-20 2-3* 10-20 2-3*

Iliopsoas

-initial

-maintenance

20-40

10-20

1-2

3-5#

15-30

10-20

1-2

3-5#

CNS

-initial

-maintenance

50-80

30-50

20-40

1-3

4-7

8-14^

50-80

30-50

20-40

1-3

4-7

8-14^

Resp. tract

-initial

-maintenance

30-50

10-20

1-3

4-7

30-50

10-20

1-3

4-7

Gastrointestinal

-initial

-maintenance

30-50

10-20

1-3

4-7

30-50

10-20

1-3

4-7

Ginjal 20-40 3-5 15-30 3-5

Deep laceration 20-40 5-7 15-30 5-7

Operasi mayor

-pre-op

-post-op

60-80

30-40

20-30

10-20

1-3

4-6

7-14

50-70

30-40

20-30

10-20

1-3

4-6

7-14

Tooth extraction

-before procedure

-after procedure

50

20-40

1-3* 40

20-30

1-3*

World Federation of Haemophilia

https://www.wfh.org

Blood component replacement therapy

factor-VIII factor-IX

(unit/ml) (unit/ml) (ml)

Fresh-frozen plasma ~ 0,5 ~ 0,6 200

Cryoprecipitate ~ 4,0 - 20

Factor-VIII concentrate 25 - 100 - 10

Factor-IX concentrate - 25 - 35 20

Faktor pembekuan

•Faktor VIII • Setiap pemberian 1 unit F VIII akan menaikkan kadar

dalam plasma sebesar 2 %• Half life 8 – 12 jam : pemberian tiap 12 jam

•Faktor IX• Setiap pemberian 1 unit F IX akan menaikkan kadar dalam

plasma sebesar 1 %• Half life 24 jam : pemberian tiap 24 jam

Contoh :

• perdarahan sendi yang berat

• perdarahan otot luas

• deep hematoma

• Perdarahan saluran kemih

Pemberian faktor pembekuan

• Periksa kandungan faktor pembeku darah yang tersedia dalam kemasan, • 250/500/750/1000 IU, tergantung dari produk

yang digunakan.

• Tanggal kadaluarsa (expired date).

• Gunakan seluruh isi botol (vial), kecuali dokter atau tim hemofilia rumah sakit menganjurkan hallain.

• Jangan gunakan faktor pembeku darah jika : • Tidak dapat larut dengan baik

• Cairan berwarna atau berubah warna

Organ Deskripsi

Mata Konjungtiva tampak pucat, sklera tidak ikterik

Ekstremitas Akral hangat, CRT <2 cm, terdapat benjolan pada dorsal pedis sinistra, diameter

8x7x7cm, batas tidak tegas lingkar kaki terbesar 48 cm, dolor, kalor, tumor, rubor

Lain-lain Dalam batas normal

Keluhan utama: benjolan di punggung kaki kanan sejak 1 bulansebelum masuk rumah sakit (suspek osteosarcoma)

An. DA, Laki-laki, 16 tahun

Pemeriksaan Radiologis

• Destruksi tulang pada metatarsal

I, os cuneiforme intermedius & m

edial serta phalang proksimal di

giti I pedis kanan dengan pe

nipisan korteks & gambaran end

osteal scalopping

• Disused osteoporosis.

Pemeriksaan Laboratorium

Laboratorium Nilai

Rujukan

Hb (g/dl) 5 12,5 - 16,1

Hematokrit (%) 27,4 36,0 - 47,0

Leukosit (/UL) 6.780 4.00 - 1050

Trombosit (1000/UL) 520.000 150 - 400

MCV (fl)

MCH (pg)

MCHC (g/dL)

70,9

26

32

78,0 - 95,0

26,0 - 32,0

32,0 - 36,0

APTT (detik) >180 33,6

PT (detik) 12,4 10,4

SGOT/SGPT (U/L) 12/15 <20/<25

Ur/Cr (mg/dL) 20/0,5 15-40/0,5-1,5

Pemeriksaan yang diperlukan

• Pemeriksaan kadar faktor VIII dan IX

• Pemeriksaan kadar faktor pembekuan dapat dilakukan paling cepat 3 hari setelah pemberian faktor pembekuan darah atautransfusi darah

• Factor assay

– Faktor VIII : 176,1% (N: >50%)

– Faktor IX : 1% (N: >50%)

• Profil besi

– Ferritin : 23,5

– Serum iron : 27

– TIBC : 379

– Saturasi transferin : 7%

Pemeriksaan MRI

Sugestif gambaran pseudotumorhemofilia di phalang proksimal digiti I, metatarsal I, os cuneiform dan os talus dengan keterlibatan jaringan lunak di

sekitarnya. Osteopenia.

Resume Kasus

Riwayat Penyakit

* Perdarahan berulang:

(Memar, perdarahan

gusi)

* Riwayat perdarahan

dikeluarga

Pemeriksaan fisis

Benjolan pada dorsal pedis sinistra, diameter 8x7x7cm, batas tidaktegas lingkar kaki terbesar 48 cm, dolor, kalor, tumor, rubor :

PSEUDOTUMOR

Pemeriksaan Penunjang

Anemia

Pemanjangan APTT

Profil besi rendah

Pseudotumor

Diagnosis Kerja

✓Hemofilia B berat

✓Hematoma (pseudotumor) regio plantar pedis

✓Anemia defisiensi besi ec perdarahan

Kegawatan

Anemia: Hb 5 g/dL

Oksigen 1 ltr/mnt nasal

Transfusi

Target Hb 9 - 10 g/dL

Delta HbxBBx4

Transfusi I : 5 ml/KgBB dalam 4 jam

Transfusi II: sisa dari perhitungan

Preparat besi

Kadar Hb & ferritin normal

Tata Laksana Perdarahan

1. Konsentrat faktor pembekuan darah

gold standard (konsentrat F IX)

alternatif :

2. Transfusi komponen darah sesuai jenis

hemofilia yang dialami (FFP)

Comprehensive care

To be governed through multidiscipline approach involving experts in the field of:

• hematology • occupational therapy

• orthopedics • vocational therapy

• infectious disease • psychology

• nutrition • nursing

• dentistry • genetics

Panduan Home treatment

Perawatan Hemofilia Mandiri di Rumah

Tim Pelayanan Terpadu HemofiliaRSUPN Dr. Cipto Mangunkusumo

2017

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