2. INTRODUCTION
• An ever increasing number of patients with established
RF are dependent on hemodialysis (HD) to sustain their
lives
• HD has very few absolute contraindications and so is the
default therapy of all forms of renal replacement
therapy (RRT).
• Long-term patient survival in incident HD patients of all
age groups has increased gradually during the past 20
years
• Adequate anticoagulation in hemodialysis procedures
relies on knowledge of hemostasis
5. HEMOSTATIC ABNORMALITIES INRENAL
INSUFFICIENCY
• Uremia can lead to increased bleeding tendency due
to PLT dysfunction
• Thrombosis can occur at increased rates in Dialysis,
PE, Vascular access thrombosis.
• Pts with Chronic renal failure have a high
prevalence of systemic inflammation & diffuse
endothelial damage
• Activation of platelets and monocytes has also been
detected
• Hypercoagulability increases as renal function declines
6. ACTIVATION OF THE COAGULATION
CASCADE IN THE EXTRACORPOREAL
CIRCUIT
• HD causes turbulent blood flow & high shear rates
• In HD, Gran & Plt coaggregation an effect which is membrane
dependent
• Co-aggregation is followed by activation of both cell types.
• On adhesion to artificial surfaces, granulocytes release the
contents of their granules
• Clotting on artificial surfaces is thought to mainly occur via the
intrinsic (contact activation)
7. ASSESSING BLEEDING RISK
• Severe thrombocytopenia (platelet count of <20,000 x 109/L
• Evidence of active bleeding
• Active intracranial or extradural hemorrhage
• Use of systemic anticoagulants
• Uremic pericarditis
• Coagulation factor VII or VIII deficiency
8. Standard-risk patients
• Both UFH and LMWH protocols are effective
• Unfractionated heparin – Dialysis units in many regions, use UFH for
anticoagulation during hemodialysis (HD). Cal-Heparine.
• We administer a bolus of 2000 units at the beginning of dialysis,
followed by a continuous infusion of 500 units per hour.
• This infusion is usually turned off 60 minutes before the end of the
dialysis session
• If clotting develops, then we stop 30 minutes before the termination
of dialysis.
9. Unfractionated Heparin
• Affects conversion of Heparin is
exerted through affecting
conversion of Fibrinogen to
Fibrin.
• Mediated by Xa as well as Iia
• It acts by activating plasma
antithrombin III
• The Heparin-ATIII complex then
to and inactivates clotting
factors. (Xa,IIa, Ixa, XIIIa)
• Intrinsic and Common Pathways
10. Low-molecular-weight heparins
• Comprise a mixture of anionic glucose-aminoglycans with a smaller
size (molecular weight: 4–8 kDa)
• Antithrombin/LMWH complexes have less affinity to thrombin
• LWMH) are the preferred initial treatment for many thromboembolic
disorders but are renally excreted and relatively contraindicated in
patients with renal failure because of concerns of increased bleeding
risks
11.
12. Patients with heparin-induced
Thrombocytopenia
• 2 forms of heparin-induced thrombocytopenia (HIT),
• Only one of which is clinically significant (type 2):
• HIT type II is a clinically significant condition resulting from
antibodies to PF4 complexed to UFH, referred to as "HIT
antibodies" or "PF4/heparin antibodies.
14. Summary
• HD and CRRT) are typically delivered with some form of
anticoagulation
• Patients on chronic HD are generally prothrombotic.
• Standard-risk patients – We treat standard-risk patients
(who are not at higher risk for bleeding or thrombosis) with
either UFH or LMWH.
• Patients at high risk for bleeding – Patients at high risk for
bleeding are treated with the "no-heparin" method
• Patients with recurrent filter thrombosis – Patients at
standard risk for bleeding who have recurrent filter
thrombosis should have their UFH or LMWH increased.
Hemostasis can be defined as a process of fibrin clot formation to seal a site of vascular injury without resulting in total occlusion of the vessel.
The initial hemostatic response to stop bleeding is theformation of a platelet plug at the site of vessel wall injury.
The intrinsic pathway, also termed the contactactivation pathway, is thought to be prominently involvedin activation of clotting on artificial surfaces such ashemodialysis membranes
The accumulation of uremic toxins causes complex disturbances of the coagulation system
Uremia can lead to an increased bleeding tendency, e.g., due to platelet dysfunction.
Uremic patients with thrombotic events show significantly higher platelet-derived microparticle counts than patients without thrombotic events
ESRD, deficiencies of the anticoagulant proteins C and S have been observed.
Activated protein C resistance can occur
Activity of the anticoagulant protein C can be decreased by inhibitors.
Activation of the TF coagulation pathway has been found.
These complex hemostatic abnormalities have been linked not only to thrombosis but also to progressive atherosclerosis, a frequent condition in ESRD patients
Shear is one major pathway of platelet-induced hemostasis and thrombosis
At slow blood flow, platelets can bind to fibrinogen adherent to the artificial surface via their GPIIb/IIIa receptor.
Receptor binding and thrombin formation due to contact activation result in the release of platelet secretion products, platelet aggregation, and activation of the coagulation cascade.
contact of blood with artificial surfaces induces profound activation of plasmatic coagulation
Patients who are on HD are generally prothrombotic and have an increased risk of clotting in the dialysis circuit.
However, the risk of bleeding exceeds the risk of clotting in certain patient groups.
An alternative approach is to customize the dose of the bolus to the patient's weight.
With this approach, a bolus of 500 IU is administered for adult patients weighing <50 kg, 1000 IU for patients weighing between 50 and 100 kg, and 2000 IU for patients weighing >100 kg.
The LMWH also bind to antithrombin.
However, because of the short chain length of LMWH, antithrombin/LMWH complexes have less affinity to thrombin, resulting in a reduced inhibition of thrombin compared with UFH.
Hemodialysis International 2007; 11:178–189
HIT type I is a mild, transient, and self-limited drop in platelet count that typically occurs within the first two days of UFH exposure.
It appears to result from non-immune platelet aggregation by a direct effect on platelets.
No change in dialysis-related anticoagulation management is warranted for HIT type 1
HIT Type 2
These antibodies can cause thrombosis and thrombocytopenia. Suspected or confirmed HIT type 2 warrants anticoagulation using a non-heparin strategy.
Boluses of isotonic saline are given every hour to minimize the degree ofhemoconcentration and to flush fibrin strands from the dialyzer into the bubble trap.
Heparinized solution rinse, or heparin-bonded dialyzer.
Most patients at high risk of bleeding are switched to a heparin-based protocol once their risk of bleeding is mitigated (eg, several days of stabilization after bleeding events or procedures)
Patients with heparin-induced thrombocytopenia (HIT) – Patients who have HIT type I do not require any changes in their anticoagulation regimen.
Patients who have HIT type II should not be treated with any UFH or LMWH products and need to be comanaged for HIT in concert with hematologists