Anticoagulation and its use in haemodialysis

Murni Indrasti
Sub Bag Nefrologi / Hipertensi Bag Penyakit Dalam FK UNDIP/RS Dr Kariadi

Basic clinical dialysis,Georgina Follows Hdx foundation

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 HEMOSTASIS

hemostasis
f
BV injury

Agregasi trombosit Konstrisi p.drh

Cascade koagulasi

Hemostasis plug stabil

HEMOSTASIS
1. Hemostasis primer; - vasokonstriksi p.drh - erbentuknya pletelet plug 2. Hemostasis sekunder - aktivasi koagulasi kaskade - deposisi dan stabilisasi fibrin 3. Hemostasis tersier - disolusi fibrin klot - plasminogen aktivasi

Hemostasis primer
1. Kerusakan dd p drh akan memaparkan protein sub endotel kolagen ke subendotel 2. Trombosit berikatan dengan kolagen melalui reseptor colagen spesifik glikoprotein 1a / 2a

Hemostasis sekunder
Kaskade koagulasi 1.Jalur intrinsik 2.Jalur ekstrinsik

Sehingga terbentuk fibrin

Hemostasis
- Hemostasis primer; trombosit segera membentuk plug pd lokasi injury - Hemostasis sekunder; terjadi bersamaan 1. faktor pembekuan dalam sirkulasi m.aktivasi kaskade kompleks 2. Membentuk fibrin strands 3 Fibrin strand memperkuat trombosit plug

Fibrinolisis; suatu proses degradasi fibrin

Plasmin akan memecah fibrin menyebabkan produksi fragmen dalam sirkulasi yang akan dibersihkan oleh bbg protease atau oleh ginjal dan hati Plasmin diproduksi dalam bentuk inaktif plasminogen didalam hati.

 Perdarahan & trombosis problem sering terjadi pd HD Perdarahan terutama disebabkan kelainan trombosit & dinding pembuluh darah walau jml trombosit sering normal, ada banyak bukti adanya defek pd glikoprotein trombosit reseptor IIb/IIIa thd fibrinogen & glikoprotein (GP) Ib vWF. Terapi antikoagulan selama HD, & penggunaan obat anti platelet sering menyebabkan tendensi perdarahan. Waktu perdarahan & kadar urea merupakan petunjuk kasar thd perdarahan. Faktor yg menyebabkan trombosis pd penderita HD yaitu : Hipotensi, Hiperhomosisteinemi, Disfungsi endotel, inflamasi, malnutrisi

 Kontak darah dgn udara pd drip chamber akan menyebabkan terbentuknya klot extrakorporeal diawali dgn timbunan & agregasi trombosit terbentuk tromboksan aII & terjadi aktifasi dari jalur koagulasi intrinsik, terjadi formasi trombin & deposisi fibrin. Pemberian heparin mencegah terjadinya klot.

Heparin akan berikatan dgn antitrombin III pd sirkulasi & menghambat faktor koagulasi I, IX, XI, XII, dan menyebabkan inaktifasi dari faktor diatas. Waktu paruh heparin 30-120 mnt & memanjang dgn adanya disosiasi heparin dari komplek antitrombin III

Faktor yg berpengaruh terjadinya klot pd ekstrakorporeal :

Low blood flow High hematocrit High ultrafiltration rate Dialysis access recirculation Intradialytic blood and blood product transfusion Intradialytic lipid infusion Use drip chambers (air exposure, foam formation, turbulence)

Pemberian heparin pd HD :

Reguler : Priming 2000 unit diikuti 1000 unit/jam, 1 jam terakhir tanpa heparin Heparin minimal : Priming 2000 unit diikuti 250 unit/jam, 1 jam terakhir tanpa heparin

Target clotting time during dialysis

Routine heparin Tight heparin

Desired range Test Reagent Baseline value

During dialysis + 80% (120-140) + 80% (200-250) 20-30 At end of dialysis + 40% (85-105) + 40% (170-190) 9-16

Desired range
During dialysis + 40% (85-105) + 40% (170-190) 9-16 At end of dialysis + 40% (85-105) + 40% (170-190) 9-16

WBPTT

Actin FS Siliceous earth None

60-85 sec

ACTa LWCTb

120-150 sec 4-8 min

WBPTT : Whole Blood Partial Thromoplastin Time; ACT : Activated Clotting Time; LCWT : Lee-White Clotting Time aThere are various methods of performing the ACT, and the baseline value with some methods is much lower, e.g 90-120 sec. bBaseline values of the LWCT vary greatly depending on how the test is performed

Komplikasi pemberian heparin

Lipid. Heparin mengaktifasi lipoproteinlipase dan meningkatkan trigliserid, menurunkan HDL kolesterol. Trombositopeni. Heparin akan menimbulkan terbentuknya antibodi - HAT1 : menurunnya jml trombosit dose dependent - HAT2 : terbentuknya imunoglobulin G thd heparin/ platelet faktor IV Pruritus Hiperkaliemi. Oleh karena supresi aldosteron

Heparin
Discovered in 1916 by McLean

Anticoagulant found in the liver

Porcine and bovine preparations Molecular weight = 3000 to 30000 Daltons

Binds to thrombin inhibitor ANTITHROMBIN III > inactivates active Factor X and inhibits conversion of prothrombin to thrombin

Basic clinical dialysis,Georgina Follows Hdx foundation

module

Advantages of Heparin
I.V. direct access

Cheap
Metabolised naturally by the liver Acts quickly and effectively on the intrinsic pathway Reversed quickly and easily by Protamine Long, established history of use

Basic clinical dialysis,Georgina Follows Hdx foundation

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Disadvantages of Heparin
Bleeding

Hyperlipidaemia
Thrombocytopenia Allergic reactions Pruritis Alopecia Osteoporosis

Basic clinical dialysis,Georgina Follows Hdx foundation

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Assessment of coagulation
Clotting times APTT (Actual Partial thromboplastin Time) or ACT (Activated Clotting Time) 120 secs Observe for signs of clotting - Darkened blood

- Streaks in dialyser
- Clots / fibrin rings in chambers - Blood entering venous isolator

- Rising / falling venous pressure

Basic clinical dialysis,Georgina Follows Hdx foundation

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Factors affecting coagulation Blood flow High haematocrit levels EPO Blood transfusion

Intra-dialytic lipid infusion

High UF rate Type of circuit Medication
Basic clinical dialysis,Georgina Follows Hdx foundation

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Factors affecting coagulation cont. Individual clotting abnormalities Type of dialyser Membrane - Natural membranes e.g. cuprophane relatively high platelet activation - Synthetic membranes vary. Polysulphone more compatible with blood than Cuprophane and Cellulose

Basic clinical dialysis,Georgina Follows Hdx foundation

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Contraindications for heparin use

Pericarditis Pre and post surgery, < 48 hour

Following temporary line insertion

Coagulation abnormalities, therapy antiplatelet Thrombocytopenia, < 150 X l0 9/L Intracranial haemorrhage Any active bleeding Uraemic patients Heparin free dialysis : flushing the dialyzer with 100ml Nacl 0,9%
Every 30-60 minute
Basic clinical dialysis,Georgina Follows Hdx foundation

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Contraindications for heparin use cont. Peptic ulcer Aortic aneurysm Cerebral aneurysm Severe liver disease

Hypersensitivity / allergic reactions

Basic clinical dialysis,Georgina Follows Hdx foundation

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Standard Heparin (UFH) Dose bolus dose 2500 U ( 50U/kgBB), maintenance 1000/jam atau initial HD: loading dose of 250-500 U followed by infusion rate 250-500, max 2000U Heparin Free Dialysis Obtain baseline clotting time

5000u heparin rinse

High blood flow rate 100-200 mls saline flush every 30 mins
Basic clinical dialysis,Georgina Follows Hdx foundation

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 L.M.W.H. inhibits Factor X, little thrombin inhibition,

APTT / ACT minimally prolonged.

Advantages

Safe, effective & decreased bleeding risk

Simple single dose required Reduced cholesterol and triglyceride levels Reduced alopecia Disadvantages

Expensive, long half life, not use ACTs

Basic clinical dialysis,Georgina Follows Hdx foundation

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BLEEDING & THROMBOSIS

Murni Indrasti
Sub Bagian Nefrologi-Hipertensi SMF Penyakit Dalam RSUP Dr Kariadi Semarang

Highlight contact with plastic tubing, the dialysis membran and air in the HD circuit stimulates the clothing cascades excessive clotting in the dialysis circuit and filter need to be discarded, in adult, this can mean the loss of 120-250 ml of blood clotting within an HD circuit can be minimised through aprpropiate use of anticoagulant therapy periodic anticoagulation is normally given during the dialysis treatment

Basic clinical dialysis,Georgina Follows Hdx foundation

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Aims and objectives To gain understanding of the mechanisms involved in the clotting process and coagulation assessment. To gain understanding of heparin, its administration, advantages and disadvantages.

To gain understanding of any contraindications to heparin uses.

To gain understanding of any alternatives to heparin usage.

Basic clinical dialysis,Georgina Follows Hdx foundation

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Introduction
Blood comes into contact with extrinsic factors during haemodialysis.

Heparin is the most commonly used anticoagulant during dialysis.

Administration of heparin

Bolus dose at the beginning of dialysis

Continuous infusion during dialysis. Both of these methods are prescribed and can be altered to tailor each patients needs.

Basic clinical dialysis,Georgina Follows Hdx foundation

module

Perdarahan pd penderita dialisis

Inadekwat dialsysis Anemi Hb < 9 Trombositopeni - Penyakit imun (SLE) - Obat-obatan misal : mycophenolate, azathioprine, ciclophospamide - Gangguan sumsum tulang Koagulopati - Heparin pd HD - Meningkatnya waktu paruh LMW heparin - Sepsis (DIC) - Post plasma varesis hilangnya faktor pembekuan

Penatalaksanaan perdarahan akut serius pd penderita HD Stop HD, resusitasi pasien Ambil darah utk crossmed & pem. koagulasi Pd penderita dgn warfarin diberikan terapi FFP (BB 80 4 unit FFP), vit K 10-20 mg i.v Pd penderita trombosit < 50.000 diberikan TC Pd penderita dgn heparin diberikan protamin 1 mg i.v tiap 100 unit heparin, dosis maksimum 50 mg dlm 10 mnt sisanya diberikan dlm per-infus dlm 8 jam Pd penderita disfungsi trombosit diberikan Desmopresin (DDAVP) DDAVP akan memobilisasi faktor VIII & vWF jaringan dari endotel Perbaikan anemi dgn transfusi sampai Hb 9 Tingkatkan dosis dialisis pd penderita dgn dialisis tak adekwat

Penatalaksanaan perdarahan AV vistula post dialisis Diberikan kompres es Bila masih berdarah diberikan DDAVP Cara pemberian DDAVP DDAVP i.v 0.3 gr/kg dlm 50cc NaCL 0.5 Waktu paruh faktor VIII plasma 5-8 jam & vWF 8-10 jam DDAVP bisa menyebabkan vasodilatasi & akan tetapi hipotensi berkurang dgn pemberian infus lambat selama 30 menit Dosis ulangan diberikan 12-24 jam setelah dosis awal

Penatalaksanaan perdarahan dari CVC Berikan tekanan lokal (dgn es) Kalau perlu dijahit Bila perdarahan msh berlanjut diberikan DDAVP Evaluasi RW pd hematom yg besar & pd hemotorax Rawat pasien

GROUP WORK
A patient complains of loss of hair over the past couple of months. She has minimal heparin on dialysis, but still no change, what would you do??

A patient has just completed dialysis and you notice that the kidney is very dark. The patient is already on high doses of heparin. What would you do??
Basic clinical dialysis,Georgina Follows Hdx foundation

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Future
Coating of elements of circuit with active heparin. Non-thrombogenic membranes. Heparinised coated cartridges capable of removing heparin infused into the extra corporeal circuit.
Basic clinical dialysis,Georgina Follows Hdx foundation

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QUESTION???

Which pathway is initiated during haemodialysis?

Basic clinical dialysis,Georgina Follows Hdx foundation

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The Coagulation Cascade

Vascular Constriction

Platelet plug formation

Formation of blood clots

Basic clinical dialysis,Georgina Follows Hdx foundation

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The Coagulation Cascade

Vascular Constriction

Platelet plug formation

Formation of blood clots

Basic clinical dialysis,Georgina Follows Hdx foundation

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Extrinsic pathway
Damaged tissue thromboplastin released initiates formation of prothrombinase in presence of Factor X and calcium ions.

The coagulation cascade then occurs by using thrombin an enzyme that converts fibrinogen into fibrin. This forms a mesh trapping the formed elements of blood thus forming a CLOT.

Basic clinical dialysis,Georgina Follows Hdx foundation

module