**5. Complications associated with use of anticoagulant therapy**

#### **5.1 Heparin-induced thrombocytopenia**

Heparin is frequently used as an anticoagulant in hemodialysis therapy due to its low cost and short half life, but a heparin-induced thrombocytopenia (HIT) is a situation restricting the use of heparin and resulting in a significant amount of mortality. HIT is classified as Type-I and Type-II.

Acute Complications of Hemodialysis 275

pericarditis with cardiac tamponade (Remuzzi, 1989; Galbusera et al. 2009). Of these, hemorrhagic stroke and subdural hematoma are more prevalent in the hemodialysis population compared to the normal population. Hemorrhagic stroke incidence is 5-10 times greater than in the normal population (Seliger et al., 2003; Toyoda et al., 2005), while the incidence of subdural hematoma was 20 times greater in a study by Power et al. For these reasons, the mortality rate in this population group is 40% higher than in the normal population (Power et al., 2010). One study regarding the frequency of hemorrhagic complications and correlation with mortality determined 48 hemorrhagic complications in 37 patients undergoing 78 continuous renal replacements. Six of the 40 major hemorrhages were intra-abdominal, 18 involved bleeding around the catheter, 3 were GIS bleeding, 12 were oronasopharyngeal and 1 intracerebral. One intracerebral case, 1 intra-abdominal case

In conclusion, the use of anticoagulant therapy in patients undergoing hemodialysis increases the tendency toward hemorrhage. The frequency of hemorrhage in vital organs in particular increases. The appropriate approach to preventing the progress of hemorrhagic complications in hemorrhagic patients during hemodialysis treatment is the restriction or avoidance of anticoagulants during hemodialysis. Systemic heparin as an alternative to anticoagulation in this patient group may be administered as regional anticoagulation with heparin and protamine, low-dose heparin, regional anticoagulation with citrate and hemodialysis without anticoagulation with intermittent saline flushes (Galbusera et al.,

Chronic hemodialysis patients are usually predisposed to hyperkalemia at the beginning of dialysis sessions. The first reason for such tendency to hyperkalemia is this patient group does not have residual urine whose major duty is to remove potassium (K) from the body. Another reason is that K passes from inside the cells to outside to correct the acid-base balance and an increase being present in nitrogenous catabolites and inhibition of these Na / K ATPase (Weiner & Wingo, 1998). K is normally in balance inside and outside the cells. A small change in K in the extracellular area causes big changes in resting membrane potential (RMP). The myocardial tissue is affected the most from this situation. A decline in RMP may result in fetal arrhythmias. For this reason, if there is a change in ECG, hyperkalemia should be treated urgently (Browning & Channer, 1981). To prevent a cardiac interaction, iv calcium may be administered. It generally starts affecting in 1 to 3 minutes; if not, a second dose may be given (Schwarts, 1978). K starts dropping after dialysis therapy begins in the hemodialysis patient group, but if the interdialytic hyperkalemia persists, dietary compatibility should be questioned in these patients. Potassium binding resins may also be

During dialysis, potassium is removed 85% by diffusion and 15% by convection. Hypokalemia is seen more often in dialysis patients and especially in those whose predialysis K levels are normal and who are administered a sodium profile technique (Buemi et al., 2009). Hypokalemia creates tendency to arrhythmia just like hyperkalemia. In order to avoid hypokalemia, the level of K in the dialysate should be arranged for each patient and the intracellular and extracellular shifts of K should be borne in mind. It is especially

and 1 with gastrointestinal bleeding died (van de Wetering et al., 1996).

2009; Yixiong et al., 2010)

**6. Electrolyte disorders** 

**6.1 Impaired potassium balances** 

given to these patients (Acker et al., 1998).

Type-I HIT is a commonly seen form. It develops as a result of a direct reaction between heparin and thrombocytes. It usually appears as a slight decline in the number of thrombocytes in the early stage of heparin administration and the number of thrombocytes goes back to normal despite the repeated heparin applications (Kapa& Qian, 2009). Type-II HIT is less common, its incidence being between 0.5 to 5% (Jang &Hursting,2005). It is an antibody immune response against platelet factor 4 and heparin complex (Visentin et al., 1994; Suranyi&Chow, 2010).

HIT generally appears with an acute systemic reaction, thrombocytopenia, thrombosis, skin necrosis and venous gangrene in the extremities 5 to 30 minutes after a bolus application of unfractioned heparin (Syed&Reilly, 2009).

In diagnosing a heparin-induced thrombocytopenia, the following criteria are used: thrombocytopenia appering 5-10 days after the initiation of heparin therapy, presence of any thrombotic event, having a normal number of thrombocytes before the heparin therapy, 50% decline in the number of thrombocytes from baseline, absence of any other reason to cause thrombocytopenia, thrombocytes returning to normal when heparin use is suspended and presence of HIT antibody seroconversion. A possible diagnosis of HIT is made after the scoring of these criteria (Warkentin, 2004).

The risk factors for developing a heparin-induced thrombocytopenia show racial differences and may vary according to the type and source of heparin used. For example, when a low molecule weight heparin (LMWH) is used, less HIT is observed as compared to the use of unfractioned heparin (UFH) (Prandoni et al., 2005). It was shown in a meta-analysis of 5 trials that unfractioned bovine heparin caused more HIT than the classical unfractioned porcine heparin (Syed&Reilly, 2009).

As the results of HIT antibodies can take time to be obtained, the treatments of high-risk patients in particular should not be delayed. When treating it, first all heparin therapies including flash and catheter lock therapies should be discontinued and then alternative nonheparin anticoagulant therapies should be initiated. However, a warfarin therapy should not be attempted until the number of thrombocytes returns to normal (Syed&Reilly, 2009). LMWH may be continued in the low-risk patients until the HIT antibody results are obtained (Warkentin et al., 2003).

Patients who developed HIT may be made subject to a non-heparin dialysis using flush or citrate anticoagulation in intervals or using the direct thrombin inhibitors lepirudin and argatroban or the Factor Xa inhibitor danaparoid (Matsuo&Wanaka, 2008, Syed&Reilly, 2009).

### **5.2 Bleeding diathesis**

Bleeding is the most important factor restricting the use of heparin in hemodialysis treatment. Taking all methods of use into account, the level of bleeding is 10%-15%, while that of hemorrhage-associated morbidity is above 15% (Davenport et al.,1994, Martin et al.,1994; van de Wetering et al.,1996) Gastrointestinal (GIS) bleeding is observed in one-third of uremic patients. Upper GIS bleeding is more frequent in uremic patients undergoing hemodialysis in particular (Galbusera et al., 2009). Kutsumi et al. reported that 17% of patients presenting to the emergency department with GIS bleeding had received hemodialysis treatment (Kutsumi et al., 1998). Other reported hemorrhagic complications include hemorrhagic stroke, subdural hematoma, spontaneous retroperitoneal bleeding, spontaneous subcapsular hematoma of the liver, intraocular hemorrhage, and hemorrhagic

Type-I HIT is a commonly seen form. It develops as a result of a direct reaction between heparin and thrombocytes. It usually appears as a slight decline in the number of thrombocytes in the early stage of heparin administration and the number of thrombocytes goes back to normal despite the repeated heparin applications (Kapa& Qian, 2009). Type-II HIT is less common, its incidence being between 0.5 to 5% (Jang &Hursting,2005). It is an antibody immune response against platelet factor 4 and heparin complex (Visentin et al.,

HIT generally appears with an acute systemic reaction, thrombocytopenia, thrombosis, skin necrosis and venous gangrene in the extremities 5 to 30 minutes after a bolus application of

In diagnosing a heparin-induced thrombocytopenia, the following criteria are used: thrombocytopenia appering 5-10 days after the initiation of heparin therapy, presence of any thrombotic event, having a normal number of thrombocytes before the heparin therapy, 50% decline in the number of thrombocytes from baseline, absence of any other reason to cause thrombocytopenia, thrombocytes returning to normal when heparin use is suspended and presence of HIT antibody seroconversion. A possible diagnosis of HIT is made after the

The risk factors for developing a heparin-induced thrombocytopenia show racial differences and may vary according to the type and source of heparin used. For example, when a low molecule weight heparin (LMWH) is used, less HIT is observed as compared to the use of unfractioned heparin (UFH) (Prandoni et al., 2005). It was shown in a meta-analysis of 5 trials that unfractioned bovine heparin caused more HIT than the classical unfractioned

As the results of HIT antibodies can take time to be obtained, the treatments of high-risk patients in particular should not be delayed. When treating it, first all heparin therapies including flash and catheter lock therapies should be discontinued and then alternative nonheparin anticoagulant therapies should be initiated. However, a warfarin therapy should not be attempted until the number of thrombocytes returns to normal (Syed&Reilly, 2009). LMWH may be continued in the low-risk patients until the HIT antibody results are

Patients who developed HIT may be made subject to a non-heparin dialysis using flush or citrate anticoagulation in intervals or using the direct thrombin inhibitors lepirudin and argatroban or the Factor Xa inhibitor danaparoid (Matsuo&Wanaka, 2008, Syed&Reilly,

Bleeding is the most important factor restricting the use of heparin in hemodialysis treatment. Taking all methods of use into account, the level of bleeding is 10%-15%, while that of hemorrhage-associated morbidity is above 15% (Davenport et al.,1994, Martin et al.,1994; van de Wetering et al.,1996) Gastrointestinal (GIS) bleeding is observed in one-third of uremic patients. Upper GIS bleeding is more frequent in uremic patients undergoing hemodialysis in particular (Galbusera et al., 2009). Kutsumi et al. reported that 17% of patients presenting to the emergency department with GIS bleeding had received hemodialysis treatment (Kutsumi et al., 1998). Other reported hemorrhagic complications include hemorrhagic stroke, subdural hematoma, spontaneous retroperitoneal bleeding, spontaneous subcapsular hematoma of the liver, intraocular hemorrhage, and hemorrhagic

1994; Suranyi&Chow, 2010).

unfractioned heparin (Syed&Reilly, 2009).

scoring of these criteria (Warkentin, 2004).

porcine heparin (Syed&Reilly, 2009).

obtained (Warkentin et al., 2003).

**5.2 Bleeding diathesis** 

2009).

pericarditis with cardiac tamponade (Remuzzi, 1989; Galbusera et al. 2009). Of these, hemorrhagic stroke and subdural hematoma are more prevalent in the hemodialysis population compared to the normal population. Hemorrhagic stroke incidence is 5-10 times greater than in the normal population (Seliger et al., 2003; Toyoda et al., 2005), while the incidence of subdural hematoma was 20 times greater in a study by Power et al. For these reasons, the mortality rate in this population group is 40% higher than in the normal population (Power et al., 2010). One study regarding the frequency of hemorrhagic complications and correlation with mortality determined 48 hemorrhagic complications in 37 patients undergoing 78 continuous renal replacements. Six of the 40 major hemorrhages were intra-abdominal, 18 involved bleeding around the catheter, 3 were GIS bleeding, 12 were oronasopharyngeal and 1 intracerebral. One intracerebral case, 1 intra-abdominal case and 1 with gastrointestinal bleeding died (van de Wetering et al., 1996).

In conclusion, the use of anticoagulant therapy in patients undergoing hemodialysis increases the tendency toward hemorrhage. The frequency of hemorrhage in vital organs in particular increases. The appropriate approach to preventing the progress of hemorrhagic complications in hemorrhagic patients during hemodialysis treatment is the restriction or avoidance of anticoagulants during hemodialysis. Systemic heparin as an alternative to anticoagulation in this patient group may be administered as regional anticoagulation with heparin and protamine, low-dose heparin, regional anticoagulation with citrate and hemodialysis without anticoagulation with intermittent saline flushes (Galbusera et al., 2009; Yixiong et al., 2010)
