HIV nursing in Poland
At the start of the HIV epidemic in the 1980s, Poland was experiencing severe economic and political crises, with martial law, food rationing, very poor supply of goods to shops, and a shortage of even the simplest cleaning items. Surprisingly, during those economically difficult years, as one HIV nurse recalls, medical staff caring for HIV patients always received the best possible equipment, and as much as was needed (much to the envy of colleagues from other specialties). The quality of gloves, bedclothes, and medical utensils designated for HIV patients was always the best. Paradoxically, due to current financial difficulties in the Polish healthcare system, this is no longer the case. Nurses now receive poor-quality equipment in comparison, and do not always feel completely protected while working.
The introduction of antiretroviral therapy (ART) has undoubtedly created a huge change for both patients living with HIV and medical staff. At present, treatment is completely free for any patient who fulfils medical and legal criteria. Post-exposure prophylaxis is also available, considerably reducing anxiety and increasing job security for doctors and nurses. So far, there has not been a single case of HIV in Poland caused by exposure in a healthcare setting.
Antiretroviral therapy gives patients better quality of life, and greater life expectancy. Patients begin to feel more secure about life, and visit the hospital more often for diagnosis or treatment. Over time, the relationship between nurses and patients develops and flourishes. As nurses observe patients’ health improvements, it makes their work easier from the psychological point of view. In the early days of the epidemic, the emotional load for nurses was much heavier when patients were passing away one by one. Nurses note now that their work brings them much more satisfaction.
The success of ART brings with it the need for long-term psychological support for the infected and their families. While the perception of HIV by healthcare professionals has changed greatly over the years–from fear to acceptance, or even viewing HIV as less contagious than, for example, hepatitis C–many myths, false beliefs and prejudices continue to flourish in general society. HIV-positive diagnoses still come as a shock for individuals and their families, and thus, there is a great need for reliable and level-headed HIV and AIDS education that is presented in a friendly environment, and in a caring way. In hospitals, this extra duty usually falls to already overstretched nurses and many do not feel sufficiently prepared to perform this task, as very little training is available. Recently, as part of its activities, the National AIDS Centre conducted 13 elementary-level workshops for 448 medical staff including nurses and midwives. Unfortunately, this was not sufficient to train all those who wished to take part. Updated guidelines for treating patients are also required.
In summary, Polish nurses who take care of HIV patients are very committed to their work and to helping their patients. However, they need more professional support, particularly in those aspects of the epidemic that are uniquely Polish.
HIV nursing in Poland
Since the beginning of the HIV epidemic, incidence and prevalence in Poland have remained at stable levels and, so far, HIV has been kept under control. The very first case of HIV infection was seen in Poland in 1985, and the first case of AIDS 1 year later. Up to the end of 2008, HIV has been diagnosed in 12,068 Polish citizens, 2189 cases of AIDS have been noted, and 962 people have died. In addition, at the end of 2008, 3822 patients were receiving antiretroviral treatment, which included 117 children. HIV patients are treated in 18 reference units (hospitals) around the country.
People living with HIV (PLHIV), and admitted to the Warsaw Hospital for Infectious Diseases, are currently dispersed to all wards. HIV-positive patients are not isolated in any way and are treated no differently from those who are HIV-negative. In Poland, medical personnel are responsible for their own and their patients’ safety and are obliged to treat all patients as potentially infected with HIV. This is a far cry from the early days of the epidemic. In 1985, the hospital was asked to prepare a place for the first Polish HIV-positive patient. The woman had come back from her job abroad and was directed to the hospital straight from the international Okecie airport, accompanied by her luggage. The nurses had been asked to turn a ward into a room exclusively for her use. All furniture and equipment was taken out, the ward was disinfected and only the most necessary items were returned. The patient was given new personal belongings, such as cutlery and towels for her use only, and all these items were cleaned and disinfected individually. She had a separate WC and a shower, again for her personal use, and she was not allowed to leave her room or be in contact with any other patients. At the time, everyone, including the medical staff, was frightened of HIV transmission.
These days, a relatively large group of HIV patients are regularly treated at the same Warsaw hospital. Over time, patients have made friends with one another and formed a strong social group. This mutual support has had a very beneficial influence on patients’ psychological states and also on the outcome of the treatment. It also ensures that nobody living with HIV feels lonely or isolated at this hospital.
Unfortunately, there are still sometimes acts of discrimination, usually by HIV-negative patients, which are a sad result of the low level of common knowledge about HIV in Poland. Generally, however, over the last 10 years, problems from stigma and discrimination have been reducing. For example, in the early 1990s, the priest Arkadiusz Nowak was unable to establish hospices for people with AIDS because there was such strong opposition on the part of local populations. Medical and nursing personnel who took care of HIV-positive patients at this time also had to cope with stigma and often preferred not to state accurately where they worked, or in which ward of the hospital. This situation can be contrasted with the events 10 years later, when, in 2000, a hospice for people with AIDS was opened in Otwock, near Warsaw, without comment. This positive shift has been brought about by social campaigns launched by, among others, the National AIDS Centre.
The patient profile is also changing. Initially, most patients had acquired HIV through intravenous drug use, but now the majority of patients are men who have sex with men (MSM). More recently, while some patients have also been infected through contaminated blood products, there are now increasing numbers of people being infected via heterosexual sex, confirming that HIV is a problem for all of us.
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Treating patients with HIV is not always easy, particularly those who have other serious problems such as drug addiction. Drug use can make a patient’s behaviour erratic and nurses can be subjected to abuse. In addition, illegal drug use can lead to serious trouble with the police and judicial system, as well as with criminal associates. Nurses often have to assist patients, especially those in hospices, with these matters, for example, helping patients to answer court summons, and even trying to trace the patient’s estranged family and friends.
People with MRSA
If people have MRSA on their hands, they can transfer it to people and objects that they touch. Other people can then pick it up on their hands and pass it on to others.
How do hospital staff stop MRSA spreading?
Hospital staff take special precautions with patients who have MRSA in order to stop it spreading to other people (see box).
Do patients have to stay longer in hospitalbecause they have MRSA?
Patients who carry MRSA do not usually have to stay longer in hospital. Patients who have an MRSA infection or any other infection may have to stay in hospital until it shows signs of clearing up. Simple hygiene measures reduce the risk of spreading MRSA. Everyone should clean their hands before and after touching patients. Hands can be cleaned with soap and water, or alcohol hand rubs. Staff will wear gloves and aprons when they care for a patient who has MRSA. Patients who have MRSA may be moved to a room on their own or into a separate area for people who have MRSA. They may stay until they have completed their course of antibiotics or they may need to continue treatment when they go home. A patient who has MRSA can go home or be cared for safely in a nursing home or residential home, using simple hygiene measures (see box).
Can MRSA harm friends and family visitingpatients in hospital?
MRSA does not usually affect healthy people. It does not usually harm elderly people, pregnant women, children and babies. But it can affect people who have serious health problems, and people who have chronic skin conditions or open wounds. Visitors can reduce the risk of spreading MRSA to other people if they do not sit on beds and if they clean their hands at the end of their visit. Nurses can give you advice, which reflects the hospital’s policy. You should ask nurses for advice if: • Someone who has a long-term health problem wants to visit a patient who has MRSA. • A patient who has MRSA wants to visit another patient in the hospital.
How is MRSA monitored?
Infection and prevention control teams monitor levels of MRSA in their own hospitals. NHS hospitals in England send information about MRSA bloodstream infections (the most serious MRSA infections) to the Health Protection Agency. The agency publishes figures for individual NHS trusts, for regions and for England (see further information). Hospital staff can compare their own progress in reducing MRSA with progress in other trusts, regionally and nationally.
What is MRSA?
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There are lots of micro-organisms (germs) on our skin and in air we breathe, the water we drink and the food we eat. Most of them are harmless, some are beneficial and a very small proportion can cause harm. Staphylococcus aureus is a common germ that is found on the skin and in the nostrils of about a third of healthy people. It can cause harm if it it enters the body, for example through cuts and sores. Meticillin (previously known as methicillin) is a type of penicillin, an antibiotic that is used to treat infections. MRSA stands for meticillin (M) resistant (R) Staphylococcus (S) aureus (A). MRSA are types of Staphylococcus aureus that have developed resistance to meticillin and some other antibiotics used to treat common infections. Strains of MRSA were first found in the 1960s following the widespread use of antibiotics (including meticillin), and occur in many countries. Some people carry MRSA on their skin or in their nostrils quite harmlessly. Some people carry MRSA for just a few hours or days, but other people carry MRSA for weeks or months. They don’t know that they carry MRSA because they have no symptoms and it does not harm them. This is called ‘colonisation’. MRSA and other germs cause problems in hospitals. Complicated medical treatments, including operations and intravenous lines (drips), provide opportunities for germs to enter the body. MRSA and other types of Staphylococcus aureus can cause local skin infections such as boils and, in more vulnerable patients, they can cause more serious infections in wounds, bones, lungs and blood (bloodstream infections).
People who carry MRSA do not look or feel different from anyone else. The MRSA does not harm them and they have no symptoms of infection. When patients come into hospital, a nurse may take swabs for laboratory tests to check for MRSA. Patients who have an infection may develop signs and symptoms, such as a high temperature or a fever. An infected wound may become red and sore and discharge pus. Many different germs can cause these signs and symptoms. Laboratory tests can show whether MRSA or other germs are the cause. A nurse may take swabs from different parts of the patient’s body to check if MRSA is present. People who carry MRSA or have an MRSA infection can be treated with antibiotics. Hospitals have policies for treatment and these policies vary according to the local situation, the condition of the individual patient, and if the patient is likely to need further or repeated hospital care. You can ask your nurses about local policies. A patient who carries MRSA may be treated with antiseptic shampoo and body wash, which reduce or remove MRSA from hair, skin and nostrils. A patient who is infected with MRSA is usually treated with an antibiotic which is given through an intravenous line (drip).
Recent Trends from Laboratory Reporting
Since 1995, laboratories across England and Wales have voluntarily reported positive diagnoses of gonorrhoea (LabBase II). This provides an insight into the epidemiology of gonorrhoea in all sites where it is diagnosed, including non-GUM settings. During 2005, 14,740 diagnoses of gonorrhoea were reported in LabBase II compared to 14,536 in 2004, an increase of 1%. A substantial decrease of 15% in the number of diagnoses was previously noted between 2003 and 2004.
Although there was an annual increase of four percent (from 8,882 to 9,238) of gonorrhoea diagnoses among men, there was an annual decrease of two percent (from 5,370 to 5,280) among women in 2005. The highest number of reports in 2005 was seen in the 25 to 34 years group for men and the 16 to 19 year group for women. An increase in the number of diagnoses was observed in all male age groups except in the 16 to 19 years group, which showed a decrease of 13% (from 1,202 to 1,051) in 2005. The number of diagnoses decreased in all female age groups bar the 35 to 44 age group which showed an increase by 17% (from 274 to 321) in the same year.
In accordance with the KC60 data, the LabBase II figures shows that London is the region with the highest number of diagnoses reported (3,876 in 2005), accounting for 26% of the total diagnoses made. Yorkshire and the Humberside, East Midlands, North East, North West, and London regions have all shown an increase in the number of gonorrhoea diagnoses between 2004 and 2005. As LabBase II is a voluntary reporting system the proportion of diagnoses reported may reflect laboratory participation rather than disease burden.
Recent trends in population sub-groups
Rates of gonococcal infection tend to be higher in urban and deprived areas and among certain population subgroups: MSM, young women, and some black ethnic populations. The high rates of gonorrhoea observed in urban areas partly reflect the distribution of these risk groups, access to care and assertive patterns of sexual mixing.
In 2005, 4,039 diagnoses of gonorrhoea reported from GUM clinics in England, Wales and Northern Ireland were homosexually acquired, an increase of nine percent since 2004. This accounts for 30% of all male diagnoses in the same period. Since 1995, the annual diagnoses of gonorrhoea among MSM showed gradual increases in the all age groups, with the highest number of infections observed in the 16 to 24 age group throughout. The increasingly high rates of gonorrhoea in MSM probably reflect increases in high risk sexual behaviour, with many MSM reporting more sexual partners and unsafe sex than previously [6]. Moreover, rectal diagnoses of gonorrhoea among men reported to LabBase II increased by 23% (from 459 to 566 positive isolates) in 2005 compared to 2004.
Young people are disproportionately affected by gonorrhoea. In 2005, young men aged 16 to 24 years accounted for 40% (5,299/13,406) of all diagnoses in men, and young women aged 16 to 24 years accounted for 70% (3,690/5,259) of all diagnoses in women. These figures are likely to underestimate the population prevalence as gonorrhoea is frequently asymptomatic in women, who may therefore not attend a clinic for testing.
Ethnicity data are not routinely collected as part of the KC60 dataset but it is available from the Gonoccoccal Resistance to Antimicrobials Surveillance Programme (GRASP). Data from GRASP highlights the disproportionate burden of gonorrhoea found among black and other ethnic minorities. High rates of gonorrhoea in these groups are likely to result from a number of factors. Sexual attitudes and behaviours vary considerably across ethnic groups and in social economic status, and access to, and use of healthcare services.
A gradual decrease in the number of diagnosis of gonorrhoea over the last few years has been observed. Diagnosis of gonorrhoea is increasing among MSM and the highest burden of infection continues to centre on young people and certain ethnic minority groups. The ongoing development of enhanced surveillance is therefore essential to permit the collection of behavioural, demographic and microbiological data in multiple settings, necessary to provide a more accurate assessment of the changing epidemiology of gonococcal infection, and enable effective allocation of future preventive efforts.
Recent trends in gonorrhoea
This report summarises the recent epidemiology of uncomplicated gonococcal infection in England, Wales, and Northern Ireland using information from two data sources; aggregated diagnoses made in genitourinary medicine (GUM) clinics, and voluntary reports of laboratory diagnosed Neisseria gonorrhoeae.
N. gonorrhoeae is the second most common bacterial STI in the UK. Men are more likely to show signs of infection such as urethral discharge, whereas most women show no symptoms and so can be unaware of their infection. As with genital chlamydial infection, women can develop pelvic inflammatory disease, which can lead to chronic abdominal pain, infertility and ectopic pregnancy. In men, local complications include epididymitis, urethral stricture, and acute prostatitis.
Recent trends from GUM reporting
In England, Wales, and Northern Ireland, national data on gonorrhoea diagnoses are based on statistics submitted to the Health Protection Agency Centre for Infections, Communicable Disease Surveillance Centre Wales and Communicable Disease Surveillance Centre Northern Ireland from GUM clinics on the KC60 statistical return. Between 1995 and 2002 the total number of gonorrhoea diagnoses in England, Wales, and Northern Ireland has more than doubled, rising from 10,186 diagnoses in 1995 to 24,918 in 2002. Since 2002 there has been a gradual decrease in the diagnoses of gonorrhoea. In 2005, 18,665 gonorrhoea infections were diagnosed in GUM clinics, a decrease of 14% since 2004 (from 21,597 to 18,665) in England, Wales, and Northern Ireland. This comprised of an 11% decrease among all men (15,093 to 13,406), of which 18% were among heterosexual men (11,375 to 9,367), and a 19% decrease among women (6,504 to 5,259). However a 9% increase in gonorrhoea diagnoses was seen among men who have sex with men (MSM) (3,718 to 4,039).
Rates of diagnosis of gonorrhoea have decreased in all age groups since 2002. The rate of diagnosis by age group has not varied over time, with the highest rates observed among men aged 20 to 24 years (213/100,000) and women aged 16 to 19 years (145/100,000) in 2005.
In 2005, London accounted for the highest percentage of new diagnoses of gonorrhoea in both men (38%) and women (30%). Among MSM, over half (55%) of diagnoses reported in GUM clinics in England and Wales were from London. Rates of diagnoses were also much higher in London than elsewhere
in the UK at 139/100,000 in men and 43/100,000 in women. Outside London, the highest rate in men was in the Yorkshire and Humberside and the North West regions (49/100,000). Rates in women outside London were highest in the Yorkshire and Humberside region (25/100,000). All regions show a decrease in the rate of gonorrhoea diagnoses between 2004 and 2005. Northern Ireland, showed an annual increase from 13/100,000 to 19/100,000 in men and from 2.2/100,000 to 2.3/100,000 in women. However, Northern Ireland remains the country with the lowest rate of gonorrhoea diagnoses for both men and women.
Valganciclovir and Human Herpesvirus–8
Ganciclovir is a nucleoside analogue of guanosine and is the mainstay of treatment against human cytomegalovirus (CMV), a γ‐herpesvirus. Ganciclovir is phosphorylated by herpes simplex virus thymidine kinase or the protein phosphokinase (UL97) of cytomegalovirus to form ganciclovir monophosphate. Cellular kinases then form ganciclovir triphosphate, which is a potent inhibitor of viral DNA polymerase. Ganciclovir triphosphate is an effective inhibitor of CMV replication, but it is not a chain terminator like acyclovir. In the presence of ganciclovir triphosphate, viral DNA replication is greatly slowed, but small fragments of CMV DNA around the origin of DNA replication continue to be made and ganciclovir monophosphate is incorporated into these small fragments of CMV DNA.
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In clinical use, human CMV can become resistant to ganciclovir and resistance mutations are found in 2 CMV genes, the UL97 protein phosphokinase and the CMV DNA polymerase. The ganciclovir resistance mutations in the UL97 gene cluster at amino acids 460 and 520, as well as from 590–607. A ganciclovir‐resistant mutation results in a UL97 protein that is unable to phosphorylate ganciclovir. Only 6% of orally administered ganciclovir is bioavailable, which greatly restricts its oral use. By attaching a valine ester to ganciclovir (valganciclovir), the bioavailability of the orally administered drug is greatly increased to 68%. A valine esterase in the human gastrointestinal mucosa cleaves the valine and results in ganciclovir in the portal blood circulation. A daily oral dose of 900 mg of valganciclovir twice per day is equivalent to an intravenously administered dose of ganciclovir of 5 mg/kg twice per day.
Sexually Transmitted Diseases
The article by Casper et al. in this issue of the Journal provides evidence that valganciclovir can also inhibit replication of human herpesvirus–8 (HHV‐8), another γ herpesvirus. Ganciclovir has been shown to be phosphorylated in the presence of both the HHV‐8 thymidine kinase and the HHV‐8 phosphotransferase (ORF36). Two other reports, however, provide conflicting evidence, which suggests that the thymidine kinase of HHV‐8 does not phosphorylate ganciclovir. It is not completely clear, therefore, how ganciclovir is activated to ganciclovir triphosphate during HHV‐8 infection. Phosphorylation by a cellular enzyme remains a possibility. It has also been shown that ganciclovir, cidofovir, and foscarnet inhibit the production of HHV‐8 from latently infected cell lines upon stimulation, whereas acyclovir has little or no activity.
The possibility that ganciclovir or valganciclovir might inhibit HHV‐8 replication and prevent development of Kaposi sarcoma in HIV‐infected patients was suggested by the observation that patients who received 4.5 g daily of orally administered ganciclovir to prevent development of CMV retinitis in the eye without an ocular ganciclovir implant also had a lower incidence of Kaposi sarcoma in a large clinical trial. This suggested the intriguing possibility that replicating HHV‐8 expressed lytic proteins or stimulated cellular cytokines, which contributed to the development of Kaposi sarcoma. It has been suggested that in KS lesions, the lytic cycle gene products may be involved in proliferation of neighboring cells, contributing to pathogenesis. One attractive candidate is an early lytic protein of HHV‐8 that might contribute to oncogenesis is the viral‐encoded G‐protein–coupled receptor of HHV‐8 (ORF74). This protein has been shown to be a viral oncogene and angiogenesis activator. The expression of ORF74 induces an angiogenesis phenotype by secretion of vascular endothelial growth factor, an angiogenesis growth factor. The HHV‐8 ORF74 can also activate mitogen-activated protein kinase, which indicates that the viral protein has a molecular specificity to trigger signaling cascades that are activated by inflammatory cytokines. Another viral protein that may be a candidate for contributing to pathogenesis is the HHV‐8 homologue of human IL‐6, the vIL‐6 protein. Thus, prevention of HHV‐8 replication might provide therapeutic benefits in human disease.
Iloprost
Iloprost, a stable prostacyclin analogue with a circulating half-life of 15 to 30 min, consistently blocks heparin-dependent platelet activation and aggregation in vitro. Intraoperative infusion of Iloprost has permitted the uneventful administration of heparin to patients with a history of HIT undergoing both vascular and cardiac surgery. At higher doses the drug may cause hypotension requiring coadministration of vasopressor support. Although, from the reports cited earlier, this agent showed considerable promise in this setting, it is unfortunately not currently available in the United States. The monoclonal antibody to the platelet glycoprotein IIb/IIIa 7E3 (Reopro) has been shown to prevent heparin-mediated platelet aggregation induced by HIT plasma in vitro. Furthermore, recent in vitro studies have demonstrated that Reopro can significantly reduce thrombin generation initiated by tissue factor. Although preliminary studies from our laboratory and others suggest Reopro is able to block the heparin-dependent antibodyinduced platelet release reactions, platelets from patients with Glanzmann’s thrombasthenia lacking the glycoprotein IIb/IIIa receptor can be activated by HIT IgG, suggesting that inhibition of this receptor will not give complete protection against the prothrombotic manifestations of the syndrome.
Other therapies. Surgical intervention such as thrombectomy or embolectomy may be indicated for limb salvage. Insertion of an inferior vena cava filter in patients with proximal deep venous thrombosis or embolism may reduce the risk of further emboli, but has been associated with thrombosis of the inferior vena cava up to the level of the filter. There have been isolated case reports of the administration of fibrinolytic agents (streptokinase, urokinase) without bleeding complications to patients with HIT with deep venous thrombosis, pulmonary emboli and arterial thrombosis. Small numbers of patients have received plasma exchange therapy in an attempt to remove the heparin-associated IgG. After relatively few treatments (ranging from one to six, generally in association with antiplatelet agents, plasmapheresis has been followed by reversal of the heparin-associated platelet aggregation abnormality, resolution of thrombocytopenia and stabilization of thrombotic phenomena. Some preparations of high dose Ig can prevent heparinassociated platelet activation by HIT sera, presumably by competitively inhibiting binding of the HIT-IgG to the platelet Fc receptor. Correction of thrombocytopenia after administration of intravenous Ig has been reported in several patients with HIT. Mexican hgh – cheap medications online.
Readministration of heparin. In patients with heparindependent antibodies, as detected by in vitro aggregation studies, reexposure to heparin is associated with a high risk of thrombocytopenia and thrombosis. In the majority of patients, the heparin-induced aggregation will disappear within several weeks, although persistence for over 2 years has been documented. In some clinical situations, such as cardiopulmonary bypass surgery, where anticoagulation is deemed essential and the safety and efficacy of heparin are well established, some investigators have advocated awaiting disappearance of the heparin-dependent antibody, as monitored by in vitro aggregation studies, and then performing the operation or procedure with full heparinization but without postoperative heparin administration. Although anecdotal, this approach has been successful. However, it may prove dangerous in those patients for whom the available in vitro assay is not sufficiently sensitive to detect a pathophysiologically potent antibody or for the occasional patient in whom severe HIT can be provoked by reexposure to heparin. HIT with thrombosis can recur years after a previous episode, even when a negative platelet aggregation test has been confirmed after the initial event. In general, patients with a history of HIT should therefore be advised to avoid further heparin exposure for life.
Conclusions
HIT is encountered more frequently in the practice of cardiology as the application of anticoagulant therapy becomes more generalized. The thrombotic complications of HIT are associated with significant morbidity and mortality and can only be prevented by early recognition of the condition. It is therefore imperative that cardiologists maintain a high index of suspicion and perform frequent platelet counts in all patients receiving heparin therapy. Once HIT is diagnosed, heparin must be stopped immediately and eliminated from all infusion lines and flushes. In most cases, alternative anticoagulant therapy should be initiated—a task made difficult at present by the absence of a readily available alternative anticoagulant agent with proven efficacy in patients with acute coronary disease. Several direct thrombin inhibitors are being evaluated in patients with HIT, and it is hoped that the margin of benefit will be sufficient to encourage the manufacturers to make this drug available for the management of this potentially lifethreatening complication of heparin therapy.
LMW heparinoid, Ancrod and Antiplatelet agents
LMW heparinoid. Although it belongs to the same family of drugs as heparin and LMW heparin, the LMW heparinoid Orgaran, which is presently available for compassionate use in the United States, differs from the LMW heparins in a number of ways. It is a mixture of sulfated glycosaminoglycans derived from porcine intestinal mucosa and consists of 84% heparan sulfate, 12% dermatan sulfate and 4% chondroitin sulfate. In contrast to LMW heparin, each component of Orgaran is structurally distinct from unfractionated heparin. As a consequence, it has relatively low cross reactivity (10% to 20%) with the heparin-dependent antibody, as determined by aggregation, serotonin release or HIPA assays. In an overview of 230 patients with HIT treated with Orgaran, 93% of patients were considered to have responded adequately to the drug during the treatment period. Approximately 26% of the patients died, but in only 7 patients (3%) was the death deemed directly attributable to Orgaran. The use of Orgaran in patients undergoing open heart surgery is potentially limited by the fact that its anticoagulant effect cannot be neutralized by protamine sulfate. Consistent with this, of 19 patients undergoing cardiopulmonary bypass surgery with Orgaran in place of heparin, 11 bled more than expected. Although Orgaran has been demonstrated to be effective in the prevention and treatment of venous thrombosis, experience in patients with acute coronary disease or in those requiring coronary or vascular surgery outside the contexts cited earlier is limited. Nevertheless, in Canada and Australia, where the drug has been licensed for clinical use for some years, most authorities currently regard Orgaran as the treatment of choice for patients with HIT (T. Warkentin, personal communication, 1997).
Ancrod. This is a rapidly acting defibrinogenating agent derived from the Malayan pit viper; it is immunologically distinct from heparin and does not cause thrombocytopenia. It acts by cleaving fibrinopeptide A from fibrinogen, producing an unstable product that is rapidly removed from the circulation. It may be administered intravenously or subcutaneously and is monitored by measuring the fibrinogen concentration. Although ancrod has been used successfully in a number of patients with thrombotic complications of HIT, it is not readily available in the United States. Furthermore, it does not suppress thrombosis in all cases (T. Warkentin, personal communication, 1997) and should therefore be considered a less favorable alternative in these patients.
Antiplatelet agents. In the absence of controlled, prospective data, antiplatelet agents such as aspirin, dipyridamole or dextran have been recommended empirically as adjunctive therapy after cessation of heparin in patients with HIT, both in the presence and absence of thrombosis. Antiplatelet agents have also been given with continued administration of heparin in patients in whom cessation of the anticoagulant agent was believed to be undesirable. In a series of 12 patients with HIT requiring urgent open heart surgery with intraoperative heparin, the preoperative administration of aspirin and dipyridamole resulted in no postoperative thromboembolic events and bleeding in only three patients. In another small study of 9 patients, however, it was found that although this strategy protected patients from thromboembolic complications, it did not prevent the thrombocytopenia associated with limited heparin reexposure. Aspirin is not consistently effective in inhibiting the heparin-dependent antibody in vitro, presumably reflecting the fact that it has an impact on only one of several pathways of platelet activation and aggregation. Furthermore, even when aspirin does prevent heparin-induced platelet activation in vitro, this does not necessarily predict its efficacy in viv.
Clinical Presentation of HIT. Part 5
Of the alternative anticoagulant therapies that have been tried in patients requiring early management for the thromboembolic manifestations of HIT, LMW heparin, the LMW heparinoid Orgaran and the defibrinogenating agent ancrod have been used most extensively. In the setting of acute coronary disease, however, the most promising therapy is direct thrombin inhibition.
Direct thrombin inhibitors. After anecdotal reports of the successful use of the prototypic direct thrombin inhibitor hirudin in the management of patients with HIT, a prospective, open-label evaluation of this drug in achieving therapeutic levels of anticoagulation in patients with HIT is under way in Europe. In a recent preliminary report on the first 82 patients enrolled in this study, effective anticoagulation was achieved in the majority. Five patients (6%) had new thromboembolic complications, 7 (8%) had major bleeding events and 3 (4%) had to undergo limb amputation.
Six patients died, but all fatal events were due to aggravation of underlying medical problems; none were causally related to hirudin. In the United States, the cost of hirudin, together with a general perception that it performed less well than expected in two recent large-scale trials in patients with acute coronary syndromes, has discouraged manufacturers from pursuing its further development for management of patients with acute coronary disease. However, these studies did confirm the safety and antithrombotic efficacy of direct thrombin inhibition, features which, together with the lack of cross reactivity with the heparin-dependent antibody, render the direct thrombin inhibitors potentially ideal alternatives for HIT. The synthetic thrombin inhibitor argatroban has been successfully used in patients with HIT. One center recently reported a reduction in mortality from 32% in untreated historical control subjects to 18% in argatroban-treated patients with HIT (107). Open-label, prospective studies evaluating argatroban in patients with a history or current evidence of HIT undergoing percutaneous coronary intervention or peripheral vascular procedures are nearing completion in the United States, and it is hoped that the margin of benefit will be sufficient to encourage the further development and marketing of this agent for the management of this condition.
LMW heparins. Several retrospective reports have shown that LMW heparin administered to patients with HIT in the absence of cross reactivity, as detected by in vitro platelet ggregation assay, results in a favorable outcome, whereas if cross reactivity is demonstrated, there is a significant likelihood of further thrombotic events. However, when sera from patients with HIT are tested for reactivity with LMW heparin using the sensitive serotonin release or HIPA assays, cross reactivity with unfractionated heparin approaches 100%. For this reason, LMW heparin therapy should be avoided in patients with HIT. However, in the absence of readily available alternatives, if the in vitro platelet aggregation assay does not demonstrate cross reactivity with LMW heparin, it is currently common practice to administer LMW heparin to these patients and monitor them closely for further thrombotic events, persisting thrombocytopenia or the development of a LMW heparin-dependent antiplatelet antibody.