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The outcome is generally favourable for those with an early onset of the disease [72] diabetes diet to follow order pioglitazone online from canada. Inthesepatients managing diabetes juicing purchase pioglitazone in india, overall survival at 5 years is reported to dka diabetes in dogs 15mg pioglitazone visa be above 80% [71 diabetes medications while pregnant buy 45mg pioglitazone amex,73,74]. A single centre study from Norway reports a 5-year surfor comparison with other proposed criteria. An expansion of these criteria macrovascular invasion and extrahepatic spread has been shown. All new models should be compared to showed 5-year survival rates at 50–70% in well-selected patients. Moreover, the presence of a latent cardiac dysfunction, forming a contrast echocardiography [102]. It should also be remembered that in most patients with resources are being wasted in attempting to do so. Electrocardiogram and transthoracic echocardiography ance between vasodilating and vasoconstrictive agents may be should be performed in all liver transplant candidates to rule out responsible for misguided angiogenesis and pulmonary hypertenunderlyingheartdisease. Some cases of transplantation in patients Recommendations: treated with these agents have been reported to be efficacious; however, long-term results are pending [107]. With increased surgical and anaesthetic expertise, considering the good outcome of elderly patients. Moreover, diabetes mellitus Cirrhotic patients with renal failure have a 7-fold increased risk is often present in obese patients and in patients with features of death, with 50% of patients dying within one month [109], of metabolic syndrome. Pre-transplant diabetes and dyslipidaemia should be reversible cause of renal failure, has to be differentiated from managed as in the general population. Osteoporosis is a common complication among patients with cirAcute kidney injury is defined as a reduction in kidney funcrhosis and most particularly in those with chronic cholestasis distion manifested by an absolute rise of serum creatinine of at least ease [118]. The evaluation of renal clearance can be difficult in patients Recommendations: with cirrhosis [111], therefore performing inulin or other exogenous marker’s clearance and renal biopsies might help in decision-making. Nutritional assessment Recommendation: Liver cirrhosis is associated with malnutrition, and cachexia is present in nearly 70% of patients with end-stage liver disease • the presence of donor-specific alloantibodies has been [113]. A screening of latent infections is required in order to treat scores in cirrhosis. To date, studies have been unable to identify a nutrievaluation of the presence of acute or chronic infections in the tional intervention that offers convincing benefits [116], and no recipient is crucial. Communitywho are from a geographic area with specific endemic infections acquired pneumonia is often caused by S. Pneumococcal vaccination is recommended the first level of screening consists of screening for human in patients with cirrhosis. Serological screening and secondary prophylaxis for coccidioidomycosis in transplant recipients have been recommended for transplant candidates and recipients in areas where these dis• A screening for bacterial, fungal and viral infections eases are endemic. Cellulitis is Anatomical evaluation the most frequent skin infection in cirrhotic patients and it has the surgeon must be warned about the type of vascularization of a recurrence rate of 20% [124]. In cirrhotic patients, bacteremia be suture-ligated during surgery or arcuate ligament are can occur spontaneously or as consequences of skin, lung or uriroutinely searched. Although transient bacteremia, associated with is indicated in cases of variant anatomy or previous hepatic therapeutic invasive procedures such as transarterial chemoemsurgery. Several studies with cirrhosis [126,127], with an increased risk of bacteremia showed that surgical thrombectomy, thromboendovenectomy Journal of Hepatology 2015 vol. Screening for prostate tions can resolve venous obstruction in liver transplant disease should be done according to the urologist indication. In accordance, the survival and the risk of mine reversibility of neuropsychiatric conditions. Common practice is to consider the patient suitable and the risk of injury to the graft. However, there are no conclusive evidence vary considerably with the type of malignancy. Whether patients who regularly use marijuana usefulness in cirrhotic patients with ascites has never been should be excluded from the waiting list remains a controversial demonstrated. An ear-nose-throat sumption of marijuana as an absolute contraindication, whereas examination associated with a nasofibroscopy, an examination 43% a relative contraindication and 10. While deceased nificant morbidity and mortality due to cardiovascular events donation is highly developed in several Southern European coun[143], increased incidence of hepatic artery thrombosis [144] tries, some Northern European countries are more advanced in and increased incidence of malignancies such as oropharyngeal the area of living donation. A further distinction can also be made between different types of deceased donation that are Recommendations: allowed and organised within a country. These two evaluation should be performed to evaluate adherence kinds of deceased donation raise different ethical concerns and of the recipient, and potential risk factors for nonrequire different organisational set-ups. The recently created Southern Alliance for Organ donation Transplantation foresees a similar collaboration. Organ donation just focusing on the exchange of a specific type of organ with a neighbouring country. However, the establishment of consplit liver) from Malta were transplanted in Italy. National provisions usually Spain and Portugal 2009: 41 organs offered to Spain from foresee that citizens (donors or relatives) can ‘‘opt-in” (explicit Portugal. Mixed solutions also exist, with or without central databases that Such organ exchanges need, for being fully operational, to be register the wishes expressed by citizens. Though to date the majority of European countries have petence (which can partially be delegated to and co-managed transplant laws based on the presumed consent principle, the with a ‘‘European Organ Exchange Organisation”). It includes practical application of national legislation particularly, with the definition of criteria to place patients on the list or exclude regard to the role of next of kin in objecting or consenting to patients from a waiting list. The lists are usually specific to the organ donation, varies substantially between countries, regions, types of organ and transplant needed (kidney, liver, lung, heart, hospitals, and even individual requestors and thus may impact pancreas, small bowel, combined transplants) and are also on ultimate efficiency of national laws. This was because of the large mining the number of deceased organ donors in a country or number of people taking paracetamol overdoses, and increasing region. Donation figures within the Eurotransplant area, however, numbers of deaths and liver transplants due to paracetamol seem to show a rather direct effect of legislative measures: donainduced hepatotoxicity. Agency, and restricted pack sizes of paracetamol to a maximum of 32 tablets in pharmacies and to 16 tablets for non-pharmacy Deceased and living donation sales. It is also the Member States’ decision on whether they organise these measures were followed by persistent significant their transplant systems based purely on deceased donation or reductions in deaths due to paracetamol overdose, with some Journal of Hepatology 2015 vol. There are 25 liver transplant teams, four which, when used in combination, have the potential to lead to of which are paediatric. This is an area of vertiginously rapid basic sciences ing list at a national level [149]. In 2013, deceased donor a significant reduction of patients needing a liver transplant for organ donation rate reached 35. Liver allocation in Spain is centre-oriented as all available Liver allocation in Europe organs are referred to the national coordinating office. There are no uniform rules or systems for organ allocation in the taskforce recommendations were implemented, which were Europe or within the European Union. Three of which also have a paeScandiatransplant (Sweden, Norway, Finland, Denmark, diatric liver transplant program. Currently, Eurotransplant (Austria, Belgium, Croatia, Germany, Hunon average, adult patients wait 142 days for a liver transplant gary, Luxembourg, the Netherlands and Slovenia) for a total while paediatric patients wait on average 78 days. The latter is an independent watchdog that proMost organisations have similar rules with an urgent priority tects public confidence by licensing and inspecting organisations group that includes acute hepatic failure and early retransplantathat store and use tissue for transplantation and other purposes. There are also similarities in allocation for children plan to change the system to a patient-oriented, national allocaand rules to favour splitting of the best liver grafts. Donor zones are allocated to each centre based on however, important differences as well. Besides allocation in elective recipients, some urgency cateCombined liver and small bowel adult recipients. Approved combined organ, which is a multiorgan liver transplant with exception of liver-kidney. Scandiatransplant is a collaboration of all Urgency status is granted only after approval by Eurotransorgan transplant centres in the Nordic countries—Sweden, Norplant, and patients in these categories are ranked by the time way, Finland, Denmark and Iceland. A pay-back systransplant centres within Scandiatransplant (two in Sweden and tem ensures that the donor centre is re-offered the next available one in each other Nordic country except for Iceland). Some systems are constructed using scores are used in conjunction with clinical and non-clinical rigorous rules based on points and scores, whereas others are parameters. The current diversity makes it unlikely that we will manage Patients with acute hepatic failure (urgent call status) have to produce a uniform organ allocation system in Europe in the priority to receive a liver from the next available deceased donor near future. All livers that Extended criteria donors were received on urgent call status or as a kind request have to be paid back to the sending centre within a 6-month period.

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Discontinuing the offending drug should be immediate if the hemolysis is drug related diabetes type 2 vegan generic 15 mg pioglitazone with amex. Other immunosuppressive or immune modifying drugs can be given depending on the patient’s status and its initial response to diabetes test best time buy 15 mg pioglitazone free shipping treatment oral diabetes medications a1c reduction buy 30mg pioglitazone overnight delivery. Anorexia and its effects on protein and lipid metabolism may play an important pathogenetic role managing diabetes and hypertension buy pioglitazone overnight delivery. Abnormal triglyceride metabolism is thought to reflect other derangements in hepatocyte functions that contribute to hepatic failure. There is no age, breed or sex predisposition, but obesity is considered a contributing factor. The common clinical features include anorexia of several days to weeks duration, lethargy and depression. The physical examination often detects a palpably enlarged smooth surfaced liver, icterus, varying degrees of dehydration, and evidence of weight loss. The clinical pathological abnormalities include a nonregenerative anemia and elevated serum transaminase, alkaline phosphatase, and bilirubin levels. Bilirubinuria is common and indicative of liver disease in the cat in the absence of hemolysis. The presence of hepatic fat deposits found on cytology specimens obtained by fine needle aspiration or histopathologically on a liver biopsy specimen are confirmative. Treatment for idiopathic hepatic lipidosis entails restoring hydration along with the provision of nutritionally balanced feedings. The latter can be accomplished with “finger feeding” baby food (without onion powder) for a short term or more efficiently through nasogastric, pharyngostomy, or gastrostomy tubes using a more nutritionally balanced ration. Ursodeoxycholic acid (Ursodiol) is a choleretic agent that increases bile flow and decreases bile toxicity. This author prefers not to use benzodiazepine tranquilizers to stimulate the appetite because of sedative side effects and their potential for hepatotoxicity in the cat. The prognosis is fair to guarded depending on whether or not the anorexia disappears and the appetite returns. Hepatic lipidosis in the dog is generally a secondary disease associated with diabetic ketoacidosis. In the cat it has 2 main types: 1) suppurative (neutrophilic) cholangitis/cholangiohepatitis and 2) nonsuppurative cholangio-hepatitis. These syndromes can be associated with other conditions such as duodenitis, pancreatitis, and cholecystitis. In the tropics, cholangiohepatitis can be caused by the liver fluke, Platynosum concinnum. Cholangiohepatitis in the dog and cat can occur with cholecystitis with the latter often becoming a surgical disorder when it becomes emphysematous or if it is associated with biliary outflow obstruction. The clinical signs include varying degrees of anorexia, weight loss, dehydration, vomiting, diarrhea, hepatomegaly, and jaundice. Fever is sometimes present especially in the cat with suppurative cholangiohepatitis and the dog with emphysematous cholecystitis. Some advocate ultrasound guided percutaneous gall bladder aspiration for culture and cytology, but this procedure in a diseased gall bladder might cause leakage and bile peritonitis. Antibiotics (ampicillin, ampicillin1 clavulanic acid, cephalosporins, and metronidazole) are strongly recommended for the suppurative form; those commonly used include those effective against gram negative and anaerobic bacteria. Ursodeoxycholic acid (Ursodiol) is a hydrophilic bile acid that has a choleretic effect and promotes the formation of nontoxic bile acids. It has to be prepared by a compounding pharmacist for a dosage of 10-15 mg/kg/day. For nonsuppurative cholangiohepatitis in the cat, prednisone is recommended at a daily dose 2. Feline liver flukes are treated with praziquantel at 20 mg/kg once daily for 3 consecutive days. The prognosis is fair to good if the condition is treated before biliary fibrosis becomes established. It can occur with cholangitis, cholangiohepatitis, or it can be due to adverse drug reactions on the liver. Other causes include various enterotoxins, sepsis, and certain inflammatory disorders such as acute pancreatitis. These conditions are managed medically along with the discontinuation of any predisposing medications, herbs, or other hepatotoxins and the treatment of the primary underlying disorder. The clinical pathological features of this group of disorders include remarkably elevated serum alkaline phosphatase, cholesterol, and bilirubin levels. Surgical exploratory is essential for an absolute diagnosis and the determination of the treatment plan and prognosis. Critical Care for the Dog and Cat in Liver Failure the main concerns in treating the dog and cat with severe liver disease are nutrition, fluid and electrolyte balance, hepatic encephalopathy, and coagulation disorders. Nutrition Oral feeding or feeding with the assistance of a pharyngostomy, esophagostomy or gastrostomy tube would be the ideal way to maintaining the patient so long as it is not vomiting. In the case of significant vomiting (more than twice/day), parenteral nutrition will have to be instituted. It is essential to provide an adequate caloric base to allow the patient to be maintained in an anabolic state. The diet should contain good quality protein and must not be restricted unless hepatic encephalopathy, hyperammonemia, or ammonium biurate crystalluria are present. In the absence of vomiting the protein requirement can be met with most available prescription diets that contain high quality protein, adequate fat and carbohydrate along with adequate vitamins and minerals to meet the cat’s daily requirements. If the cat is being tube fed the use of a blender will greatly facilitate its administration. Those on enteral nutrition will be fed commercially available liquid diets that are made of the right consistency for enteral tube administration. Sodium intake should be limited to 100 mg/100 kcal energy requirement in hypoalbuminemia and in those with ascites. The palatability from such a diet will probably suffer, and in the patient that is already anorectic, tube feeding will probably be essential. Thiamine 12 deficiency can cause a severe polioencephalomalacia and is best avoided by providing normal daily needs. Fifty milligrams can be given daily for the next few days followed by normal dietary amounts. Vitamin B (cobalamine) supplementation might help 12 cats with co-existing pancreatic and small intestinal disease. Blood cobalamine levels can be sent to a commercial laboratory and treatment can be provided with 0. Vitamin E and Vitamin K are also important nutrients that should be provided for their 1 activity against cellular oxidative injury and coagulation disorders, respectively. Fluid Therapy Fluid therapy and meticulous protocols for its administration is an essential part of caring of critical care medicine. Patients with hypoalbuminemia are very susceptible to intravenous fluid overload and should therefore be monitored closely. The special considerations concerning fluid therapy for dogs and cats with liver disease include hypovolemia, hypoalbuminemia, blood loss, predisposition to edema and body cavity effusions, and sepsis caused by breaks in sterile procedure. The tendency for sensitivity to fluid overload is because the patient with chronic liver disease can have an active renin-angiotensin-aldosterone system because of the ineffective blood volume they might have. One good way to administer parenteral fluids to such patients is to infuse a slow infusion of both crystalloids and colloids. The increased plasma oncotic pressure delivered with this fluid formulation will help restore intravascular Starling’s forces to normal by expanding intracellular volume, limiting the requirement of crystalloid, and allowing for a more prolonged lasting effect of the volume expansion efforts. It is recommended that only one third of the normal amount of crystalloid be given if a colloid is given at a dose of 10/ml/kg which is the 24 hour recommendation of Hetastarch for the cat. If either Hetastarch or Dextran 70 is used, it is important to consider their effect on the patient’s coagulation status because of their known tendency to antagonize blood clotting which is already a concern in a cat whose liver disease is already compromising hemostasis. Albumin infusions will benefit the patient with hypoproteinemia and when combined with rapid paracentesis in the ascitic patient, the procedure might avoid being complicated by lifethreatening hypovolemia. Although human albumin has been given to several dogs without allergic complications, it is safer to use same species plasma. Any foreign protein carries the threat of anaphylaxis with it thereby calling for much diligence during its administration. All allergic reactions must be met with immediate discontinuation of the plasma or albumin infusion. Dextrose-containing solutions should be used whenever the blood glucose concentration cannot be maintained within normal limits of 70-125 mg/dl.

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If the neutrophil granules are larger be seen in hereditary spherocytosis diabetes insipidus blood glucose levels purchase pioglitazone 15mg overnight delivery, hemolytic anemias than normal and stain a darker blue diabetes type 1 lifespan generic 30mg pioglitazone amex,“toxic granulations” of other causes diabetes test strips target purchase 45 mg pioglitazone overnight delivery, and clostridial sepsis diabetes prevention exercise discount pioglitazone amex. Dacrocytes are are said to be present, and they also suggest a systemic teardrop-shaped cells that can be seen in hemolytic aneinfiammation. The presence of neutrophils with more mias, severe iron deficiency, thalassemias, myelofibrosis, than five nuclear lobes suggests megaloblastic anemia. Schistocytes are helmetLarge misshapen granules may refiect the inherited shaped cells that refiect microangiopathic hemolytic Chediak-Higashi syndrome. Eosinophils are slightly larger than neutrophils, have Echinocytes are spiculated red cells with the spikes evenly bilobed nuclei, and contain large red granules. Diseases spaced; they can represent an artifact of abnormal drying of eosinophils are associated with too many of them of the blood smear or refiect changes in stored blood. They They can also be seen in renal failure and malnutrition normally total less than one-thirtieth the number of and are often reversible. Basophils are even rarer than eosinophils in cells with the spikes irregularly distributed. They have large dark-blue granules and may tends to be irreversible and refiects underlying renal be increased as part of chronic myeloid leukemia. Elliptocytes Lymphocytes can be present in several morphologic are elliptical-shaped red cells that can refiect an inherforms. Most common in healthy individuals are the ited defect in the red cell membrane, but they are also small lymphocytes with a small dark nucleus and scarce seen in iron deficiency, myelodysplastic syndrome, cytoplasm. In the presence of viral infections, more of megaloblastic anemia, and thalassemias. Stomatocytes are the lymphocytes are larger, about the size of neutrophils, red cells in which the area of central pallor takes on the with abundant cytoplasm and a less condensed nuclear morphology of a slit instead of the usual round shape. About 1% Stomatocytes can indicate an inherited red cell memof the lymphocytes are larger and contain blue granules brane defect and can also be seen in alcoholism. Target in a light blue cytoplasm; these are called large granular cells have an area of central pallor that contains a dense lymphocytes. These cells are seen classically in lymphocytes are increased in number, and many of them thalassemia, but they are also present in iron deficiency, are ruptured in making the blood smear, leaving a cholestatic liver disease, and some hemoglobinopathies. One last feature of the red cells to assess before movMonocytes are the largest white blood cells, ranging ing to the white blood cells is the distribution of the red from 15–22 µm in diameter. In most individuals, the cells lie side variety of shapes but usually appears to be folded; the by side in a single layer. Most often upon one another; it is seen in certain paraproteinemias the abnormal cells originate from neoplasms of bone and autoimmune hemolytic anemias. Another abnormal marrow–derived cells including lymphoid cells, myeloid distribution involves red cells lying in single cell rows on cells, and occasionally red cells. This is called of tumors can get access to the bloodstream, and rare rouleaux formation and refiects abnormal serum protein epithelial malignant cells may be identified. Three blood smears made from buffy coats, the layer of cells types of granulocytes are usually present: neutrophils, that is visible on top of sedimenting red cells when eosinophils, and basophils, in decreasing frequency. Bands are immature neutrophils that Figures in this chapter were borrowed from Williams Hematology, 7th edihave not yet completed nuclear condensation and have a tion, M Lichtman et al (eds). Note that the diameter of the red blood cell is Microcytes (right panel) are smaller than normal red blood similar to the diameter of the small lymphocyte nucleus. These cells are both larger than normal (mean Hypochromic microcytic anemia of iron deficiency. Small lymphocyte and segmented (multilobed polymorphonuclear leukocytes) are larger than neutrophil upper left center. Note irregular collections of normal neutrophils with five or more segmented nuclear aggregated red cells. Target cells are recognized by the bull’s-eye acanthocytes are contracted dense cells with irregular memappearance of the cell. Small numbers of target cells are brane projections that vary in length and width; echinocytes seen with liver disease and thalassemia. Larger numbers are have small, uniform, and evenly spaced membrane projectypical of hemoglobin C disease. Acanthocytes are present in severe liver disease, in patients with abetalipoproteinemia, and in rare patients with McLeod blood group. Echinocytes are found in patients with severe uremia, in glycolytic red cell enzyme defects, and in microangiopathic hemolytic anemia. Howell-Jolly bodies are tiny nuclear remnants that are normally removed by the spleen. They appear in the blood after splenectomy (defect in removal) and with maturation/dysplastic disorders (excess production). This is often seen as an artifact in a dehyTeardrop cells and nucleated red blood cells characteristic drated blood smear. A teardrop-shaped red blood cell (left anemias and in conditions in which the red cell is overhypanel) and a nucleated red blood cell (right panel) as typically drated or dehydrated. The stained material is precipitates of denatured Myelofibrosis of the bone marrow. Giant platelets, together with a marked increase in the platelet count, are seen in myeloproliferative disorders, especially primary thrombocythemia. Silver stain of a myelofibrotic marrow showing an increase in reticulin fibers (black-staining threads). The film was prepared from the buffy trophil with a sausage-shaped nucleus in the center of the coat of the blood from a normal donor. Nodular (follicular) lymmarrow (H&E stain), showing a mix of fat cells (clear areas) phoma infiltrate in a marrow biopsy specimen. The percentage of the space that is characteristic paratrabecular location of the lymphoma cells. If demands for increased marrow production occur, cellularity may increase to meet the demand. Normal hematopoietic precursor cells are virtually absent, leaving behind fat cells, reticuloendothelial cells, and the underlying sinusoidal structure. Marrow biopsy men showing a myeloid/erythroid ratio of fi3:1, suggesting specimen infiltrated with metastatic breast cancer and reaceither a loss of red blood cell precursors or an expansion of tive fibrosis (H&E stain). Leukemic myeloblast with an Auer moblasts showing a more immature-appearing nucleus with rod. Lymphocytes with frequently convoBurkitt’s leukemia, acute lymphoblastic leukemia. The central macrophage is ingesting red cells, neutrophils, and Nodules vary in size and contain predominantly small lymplatelets. Kiyomi Tsukimori, Kyushu University, phocytes with cleaved nuclei along with variable numbers of Fukuoka, Japan. Most plastic cells are heterogeneous but predominantly large cells of the cells are normal lymphocytes, neutrophils, and with vesicular chromatin and prominent nucleoli. The lighter areas are macrophages mononuclear lacunar cell with retracted cytoplasm in a attempting to clear dead cells. The distinctive red coloration of plasma (hemoglobinemia) in a spun blood sample in a patient with intravascular hemolysis. Con2 red cells and an inappropriately low reticulocyte response sequently, elaborate mechanisms have evolved that allow (reticulocyte index <2. O2 is also bound by myoglobin in nutrition and endocrine deficiencies, and anemias from muscle. Marrow damage states are discussed in enzymes, including the cytochrome system in mitoChap. Iron distribution in the body is shown in Hypoproliferative anemias are the most common Table 7-1. Without iron, cells lose their capacity for anemias, and anemia associated with acute and chronic electron transport and energy metabolism. The anemia cells, hemoglobin synthesis is impaired, resulting in aneof infiammation, like iron deficiency, is related in part to mia and reduced O2 delivery to tissue. Iron absorbed from the diet has the highest affinity for transferrin receptors; apoor released from stores circulates in the plasma bound transferrin (transferrin not carrying iron) has very little to transferrin, the iron transport protein. Although transferrin receptors are found on bilobed glycoprotein with two iron binding sites. Transcells in many tissues within the body—and all cells at ferrin that carries iron exists in two forms—monoferric some time during development will display transferrin (one iron atom) or diferric (two iron atoms).

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The findings were as follows (Slichter 1978): at a platelet count of < 5 x 109 /L: 50 mL fi 20 mL/day at a platelet count of 5 – 9 x9/L: 9 mL fi 7 mL/day at a platelet count of 10 – 25 x 109/L < 5 mL/day 9 the standard platelet transfusion trigger in the United States is 20 x 10 /L diabete type 1 cure purchase cheap pioglitazone line. Observational 9 cohort studies reported that transfusion triggers lower than 20 x 10 /L did not result in a higher incidence and/or increased severity of bleeding (Slichter 1978 blood sugar keeps going up generic pioglitazone 30 mg amex, Gaydos 1962 diabete x obesidade generic 30mg pioglitazone free shipping, Gmur 1991 diabete tipo 2 buy cheap pioglitazone online, Wandt 1998, Sagmeister 1999, Gil-Fernandez 1995, Navarro 1998, Lawrence 2001, Callow 2002, Nevo 2007a). A retrospective analysis of patients treated with a myelo-ablative allogeneic haematopoietic stem cell transplant compared patients who were transfused at a platelet transfusion trigger 9 9 of 10 x 10 /L with a historic group of 170 patients transfused at a trigger of 20 x 10 /L. In the lower trigger group there were significantly more patients with deep thrombocytopenia < 10 x 9 10 /L (19% versus 7%). In both cohorts, deep thrombocytopenia was associated with higher mortality; however, this was not due to bleeding (Nevo 2007). However, it was not demonstrated that increasing the platelet transfusion threshold to 20 x 9 10 /L had any effect on this non-bleeding related mortality. There was no correlation 9 between the platelet count and the bleeding risk at a platelet count fi 10 – 80 x 10 /L (Slichter 2010). Four randomised studies in patients treated because of a haemato-oncological malignancy 9 9 and/or stem cell transplantation compared transfusion triggers of 10 x 10 /L and 20 x 10 /L 9 9 (Heckman 1997, Rebulla 1997, Zumberg 2002) and 10 x 10 /L and 30 x 10 /L (Dietrich 2005). The same 3 studies (Heckman 1997, Rebulla 1997, Zumberg 2002) were included in the Cochrane analysis in 2004. This meta-analysis concluded that equivalence between a trigger of 10 and 9 20 or 30 x 10 /L had not (yet) been demonstrated (Stanworth 2004). At least 3 analyses of large study populations on the risk of bleeding show that it is not the platelet count but the occurrence of a bleeding in the preceding five days that is the most important risk factor for bleeding. However, in practice, the transfusion 9 threshold is increased to 20 x 10 /L almost everywhere in the case of a severe bleeding. This can be the reason that bleeding occurs primarily at higher platelet counts in these analyses. Blood Transfusion Guideline, 2011 229 229 the optimal threshold level for platelet transfusions has not been examined for patients who are taking anti-coagulant medication. However, the studies were too Level 2 small to conclude that the various triggers are equal. B Rebulla 1997, Heckman 1997, Zumberg 2002, Dietrich 2005 In patients following allogeneic myelo-ablative haematopoietic stem cell 9 transplantation, maintaining a platelet transfusion trigger of 10 x 10 /L was associated with significantly more periods of deep thrombocytopenia than 9 when a platelet transfusion trigger of 20 x 10 /L was maintained (19% Level 3 versus 7%). In both cohorts, deep thrombocytopenia was associated with higher mortality, however, this was not due to bleeding. C Nevo 2007 230 Blood Transfusion Guideline, 2011 In clinical situations that can promote bleeding (sepsis, fever, high blast count, extensive endothelial damage) consensus guidelines advise 9 increasing the platelet transfusion trigger to 20 x 10 /L. The working group deems that the number of platelet triggers 9 should be reduced (namely 10, 20, 50 and 100 x 10 /L), as there is very little evidence 9 supporting the various triggers. Therefore, the current consensus recommends 50 x 10 /L 9 for patients with an indication for anti-coagulant therapy. Although the platelet count does not appear to be related to an increased risk of recurrent bleeding in patients who have experienced severe bleeding in the preceeding 5 days, most experts still feel that for the present it is safer to increase the platelet transfusion trigger to 9 20 x 10 /L for such patients. In the case of a standard risk of bleeding, a transfusion trigger of 10 x 10 /L is recommended for prophylactic platelet transfusions. If there are additional clinical complications that promote bleeding, it is recommended 9 that the platelet transfusion trigger be increased to 20 x 10 /L for prophylactic platelet transfusions. For patients with an indication for anti-coagulant treatment, it is recommended to 9 increase the platelet transfusion trigger to 50 x 10 /L in order to prevent spontaneous bleeding; this is not evidence based. In the Netherlands, the standard component is a platelet concentrate prepared from 11 several buffy coats or apheresis, with a dose of 3 – 4 x 10. Various randomised studies compared a low, standard and high transfusion dose for prophylactic platelet transfusions (Goodnough 2001, Klumpp 1999, Norol 1998, Sensebe 2005, Tinmouth 2004). A meta11 11 analysis of these 5 studies by Cid in 2007 compared a dose of < 3 x 10 versus > 3 x 10. Blood Transfusion Guideline, 2011 231 231 Use of the higher dose resulted in a significantly longer interval to the next transfusion and a higher post-transfusion value. Since then, two randomised studies have been performed with bleeding as end point. Use of the bleeding time to determine the indication for platelet transfusions during procedures is unreliable (Lind 1991). Thorough preparation for the procedure, checking for medications that interfere with haemostasis, monitoring the level of clotting factors, discontinuing anti-coagulant medication if necessary and avoiding hypothermia of the patient are advised (Bain 2004, Valeri 2007). Mild bleeding was observed at platelet counts < 50 x10 /L, primarily increases in further bleeding of the insertion site (Doerffler 1996, Mumtaz 2000, Ray 1997). Another study found no relationship between bleeding and a platelet count of 6 – 9 37 x 10 /L (Stecker 2007). The largest series reported no increase in bleeding 9 during ultrasound-guided biopsies, despite a platelet count < 50 x 10 /L, with or without additional clotting abnormalities (Caturelli 1993). Most guidelines advise a platelet count > 9 50 – 80 x 10 /L for percutaneous liver biopsy. High risk operations 9 Various guidelines advise platelet target values > 100 x 10 /L for high risk operations, such as heart, brain or eye surgery (excluding cataract surgery). These target values were not based on comparative research with bleeding as end point. As revision of the recent 9 literature found no indications that more or fewer bleeds would occur at 40 versus 60 x 10 /L 9 and a platelet count of 50 x 10 /L is recommended as trigger/threshold value elsewhere in 9 this guideline, the working group has decided to maintain a platelet count of 50 x 10 /L 9 9 instead of 40 or 60 x 10 /L. As to bleeding in enclosed spaces of vital organs – such as brain, nervous system 9 and eye – the aim is often to increase the count to > 100 x 10 /L. With respect to bleeding in enclosed spaces of vital organs – such as the brain, the nervous system and the eye – the advice is to transfuse platelets to a platelet count 9 of >100 x 10 /L. Transfused platelets are broken down more rapidly – in the same way as autologous platelets – due to the presence of autoantibodies. Platelet transfusions may be necessary if there is no response or if there is a need for emergency surgery such as a splenectomy. The aim is to achieve a non-traumatic birth, particularly in the interests of the child. The cause of this is a strong reaction by platelet-specific alloantibodies that reach a high titre in a short period of time, with the autologous platelets being broken down as innocent bystanders. This is because it may promote thrombotic complications (Swisher 2009, Harkness 1981; Lind 1987; Bell 1991; Kennedy 2000). Elective procedures should be postponed as long as possible, until treatment of the underlying disease has started. Non-evidence based guidelines advise to aim for > 50 x 10 /L 9 platelets for a Caesarian section and > 20 x 10 /L for a vaginal delivery (Van Dam 1989, Sibai 1990, Sibai 2004, Baxter 2004, Haram 2009). Corticosteroids (particularly antenatally administered dexamethasone) improve the platelet count more quickly, without affecting the clinical outcomes for mother and child (Woudstra 2010). In the absence of clear gain on clinical outcomes, Level 2 corticosteroids are not recommended as a matter of routine. Whether a vaginal delivery is aimed for or not, one should always consider that an indication for a Caesarian section may arise, it is therefore recommended to keep the platelet count 9 during childbirth > 50 x 10 /L (the recommended platelet count for a Caesarian section). According to the Dutch guidelines, this platelet count is also suitable for the use of epidural 9 analgesia. If it is decided to give platelet transfusions, the recommendation is to start preferably with the administration of plasma. In large series, thrombotic complications are listed more frequently than bleeding complications (Shantsila 2009). However, in patients on the intensive care unit, Blood Transfusion Guideline, 2011 239 239 severe internal bleeding was described in more than 50% of the patients, possibly due to anti-coagulant therapy that was too aggressively titrated (Wester 2004). However, confirmed cases of thrombosis have not been described, whilst there have been case reports in which bleeding (in 4 patients) was stopped after platelet transfusion without thrombotic events (Hopkins 2008). Other considerations With normal spleen size, approximately 1/3 of the platelets are withdrawn from circulation. In the case of splenomegaly – depending on size and cause – this part can increase to 90%. In the case of an enlarged spleen, the platelet dose should be increased in order to achieve the desired increment or to stop bleeding. Depending on the size of the spleen, 2 – 4 times the standard dose should be administered for a therapeutic transfusion. As a general rule, prophylactic platelet transfusions are not indicated, unless there is also thrombocytopenia. Anticipation of any bleeding during procedures and treatment of manifest bleeding is essential. Blood Transfusion Guideline, 2011 241 241 Uraemia In 75% of patients with uraemic thrombocytopathy, the bleeding time is corrected after administration of Desmopressin.