Cryoprecipitate is indicated for the treatment of fibrinogen deficiency or dysfibrinogenaemia when there is clinical bleeding, an invasive procedure, trauma or disseminated intravascular coagulation. Local clinical protocols should be followed. If in doubt, discuss with your Haematologist or a Lifeblood Medical Officer.
Typically one unit of whole blood derived cryoprecipitate per kg body weight would be expected to increase the fibrinogen concentration by 0. Taken together, DIC is the most probable explanation for the coagulopathy in this patient. One of the often-advocated laboratory tests for the diagnosis of DIC, fibrinogen, is therefore not a very good marker for DIC, except in very severe cases, although sequential measurements can give some insight.
Dynamic changes in coagulation factors and platelets may add important information. A significant drop in platelet count as illustrated in this case , a lengthening duration of clotting assays, or an increase in fibrin split products, even still within the normal range, can indicate an early stage of developing DIC.
There is no single laboratory test with sufficient accuracy for the diagnosis of DIC. This scoring system is only appropriate in patients with an underlying disorder that can be associated with DIC. Flowchart for the diagnostic and therapeutic management of DIC. LMW, low molecular weight. In our patient, the platelet count 1 point , prolongation of the PT 1 point , and strongly increased D-dimer 3 points led to a score of 5 points, compatible with a diagnosis of DIC.
A year-old woman, with long-standing alcohol abuse, presented with decompensated liver cirrhosis. At physical examination, the most prominent signs were hepatic encephalopathy, jaundice, splenomegaly, and ascites.
Laboratory test results showed a hemoglobin concentration of 7. The question is whether these coagulation abnormalities are due to liver failure-related coagulopathy or DIC, secondary to an infection.
In patients with severe hepatic failure, several changes in coagulation may occur. The combination of thrombocytopenia and low levels of coagulation factors was traditionally interpreted as a hypocoagulable state and associated with a high risk of bleeding.
However, recent insights point to a rebalanced hemostatic system in patients with chronic liver failure, as low levels of natural coagulation inhibitors may balance low levels of coagulation factors and the reduced platelet count may be offset by high levels of von Willebrand factor.
The differential diagnosis between the coagulopathy of liver disease and DIC is challenging as many laboratory abnormalities point in the same direction. Even more complex situations may occur when the coagulopathy of liver disease is complicated by DIC, as patients with severe liver disease may present with infectious complications such as bacterial peritonitis or leakage of endotoxin from the intestinal compartment that may elicit DIC. However, in most cases, the coagulopathy of liver disease can eventually be distinguished from the presence of DIC.
In the case presented, the DIC score was 4 suggestive of no DIC , and, in combination with the clinical signs and symptoms, a diagnosis of coagulopathy due to severe liver failure was made. A year-old man presented with severe cholangiosepsis due to an obstructive stone in the common bile duct. He was in shock, respiratory insufficient, and developed acute renal failure. Blood cultures were positive for Klebsiella pneumoniae.
Awaiting endoscopic retrograde cholangiopancreatography and restoration of bile duct patency, the patient was treated with vasopressors, intubation, and mechanical ventilation, and antibiotic treatment was started. The question is what would be the most appropriate supportive treatment of the coagulopathy. The keystone in the management of DIC is adequate treatment of the underlying disorder. If the condition causing the DIC is properly dealt with in the example of the case with bile duct drainage and antibiotics , the coagulopathy will spontaneously resolve.
However, in some situations, adjunctive supportive treatment aimed at the coagulation system will be required, because the coagulopathy may proceed for a while even after adequate treatment of the underlying condition has been initiated Figure 2. Low levels of platelets and coagulation factors may increase the risk of bleeding, in particular in postoperative patients or those planned to undergo an invasive intervention.
However, plasma or platelet substitution therapy should not be instituted on the basis of laboratory results alone; it is indicated only in patients with active hemorrhage and in those requiring an invasive procedure or who are otherwise at risk for bleeding complications.
The use of large volumes of plasma may be required to restore normal levels of coagulation factors. Coagulation factor concentrates, such as prothrombin complex concentrate, may overcome this impediment, but these agents may lack important factors eg, factor V.
Previously, the use of prothrombin complex concentrates was thought to aggravate the coagulopathy in DIC due to small traces of activated factors in the concentrate.
It is, however, not very likely that this is still the case for the currently available concentrates. Specific deficiencies in coagulation factors, such as fibrinogen, may be corrected by administration of purified coagulation factor concentrates. Vitamin K must be remembered as a useful non—blood product alternative to correcting vitamin K—dependent factors and will work within 4 to 6 hours after a dose.
Experimental studies have shown that heparin can at least partly inhibit the activation of coagulation in DIC. Restoration of the levels of physiological anticoagulants in DIC may be a rational approach and has been extensively evaluated. All trials have shown some beneficial effect in terms of improvement of laboratory parameters or even improvement in organ function. An international multicenter, randomized controlled trial with an anti-thrombin concentrate, however, did not demonstrate a significant reduction in mortality of septic patients.
Adjunctive therapy with activated protein C APC has also been widely studied. A phase III trial of APC concentrate in patients with sepsis was prematurely terminated because of a significant reduction of mortality in these patients. The last large placebo-controlled trial in patients with severe sepsis and septic shock was prematurely stopped due to the absence of any significant advantage of APC. A promising intervention that is currently being evaluated is recombinant soluble thrombomodulin.
Preclinical experimental sepsis studies have demonstrated that soluble thrombomodulin is capable of ameliorating the derangement of coagulation and may improve organ dysfunction. The encouraging results with soluble thrombomodulin were confirmed by retrospective data in large series of Japanese patients and are being prospectively investigated in a currently ongoing multicenter phase III trial.
A year-old female presented with severe persisting epistaxis. She also reported gingival bleeding and widespread ecchymosis for 1 week and unusually severe menorrhagia. Laboratory analysis showed a hemoglobin concentration of 5.
Taken together, these results indicate the presence of DIC in combination with marked hyperfibrinolysis. There is ample evidence for a procoagulant state in virtually all patients with advanced malignant disease.
This may eventually lead to venous thromboembolism or evolve into DIC. A special manifestation of DIC may occur in some patients with advanced adenocarcinoma, but more frequently in patients with acute promyelocytic leukemia AML-M3 and monocytic leukemias eg, the M5 subunit of AML at the time of diagnosis.
In cases of DIC where thrombosis predominates, such as arterial or venous thromboembolism, severe purpura fulminans associated with acral ischemia or vascular skin infarction, therapeutic doses of heparin should be considered. In these patients where there is perceived to be a co-existing high risk of bleeding there may be benefits in using continuous infusion unfractionated heparin UFH due to its short half-life and reversibility.
Weight adjusted doses e. Monitoring the APTT in these cases may be complicated and clinical observation for signs of bleeding is important. In critically ill, non-bleeding patients with DIC, prophylaxis for venous thromboembolism with prophylactic doses of heparin or low molecular weight heparin is recommended.
In a study of cryoprecipitate use in Canadian hospitals, a mean dose of 7. There have also been widespread reports of inappropriate dosing of cryoprecipitate.
In a cohort of massively transfused trauma patients who received no other blood products in the 2 h before cryoprecipitate transfusion , a dose of 8. Most guidelines recommend that cryoprecipitate be administered in response to fibrinogen levels decreasing below a certain threshold; however, in an emergency setting, turnaround times for the Clauss fibrinogen assay are too long to effectively guide administration of haemostatic therapy in patients with acquired coagulopathic bleeding.
In an attempt to address this issue, Chandler and colleagues proposed a revised fibrinogen assay in their emergency haemorrhage panel. Furthermore, viscoelastic methods such as ROTEM and thrombelastography TEG can be performed at the bedside and provide rapid assessment of multiple coagulation parameters.
For each of these methods, a specific fibrin test is available FIBTEM and the functional fibrinogen test, respectively. Point-of-care monitoring may prevent over- and under-dosing, potentially reducing side effects and costs while ensuring that patients are given sufficient coagulation therapy. Point-of-care tests are effective for guiding targeted haemostatic therapy; there is growing evidence that their use is associated with lower transfusion requirements for allogeneic blood products in a variety of clinical settings.
Although there is a growing body of literature on the use of viscoelastic tests to guide the administration of coagulation factor concentrates, few studies have been published on their use to guide administration of cryoprecipitate. In contrast, fibrinogen concentrate is reconstituted as a smaller volume, which allows large doses to be administered in a few minutes.
Cost is highly influential in decision-making policies. Cryoprecipitate is generally perceived as being cheaper than fibrinogen concentrate; however, the true cost of blood products such as cryoprecipitate is higher than the direct acquisition cost of the drug: indirect costs must also be taken into account. Following manufacture, indirect costs include storage, preparation, thawing, processing, and compatibility testing.
Moreover, blood products are wasted if they cannot be used as planned, and haemovigilance schemes must be maintained. Transfusion of cryoprecipitate is also affected by the cost of treating adverse events , and infectious disease associated with transfusion. Further developments may address one of the main concerns regarding the use of cryoprecipitate, namely the risk of pathogen transmission.
Pathogen inactivation steps have previously been described for the production of FFP, and recent studies have described the production of cryoprecipitate from plasma treated with riboflavin and UV light, amotosalen and UV light and solvent-detergent filtration. Fibrinogen concentrate may provide a favourable alternative to cryoprecipitate, such as is currently practiced in most of the EU.
It can be stored at room temperature, is readily available for use, and is easy to reconstitute and administer. Fibrinogen concentrate also undergoes virus removal and inactivation steps, which have been shown to be effective against both enveloped and non-enveloped viruses. Results from recent clinical studies show promising efficacy of fibrinogen concentrate in various clinical settings. Current guidelines specify that coagulation factor concentrates should be used in preference to cryoprecipitate for the treatment of haemophilia A and von Willebrand disease because of safety reasons 13 , 86—89 Table 2.
Thus, local licensing and availability largely dictates in which countries cryoprecipitate and fibrinogen concentrate are used. It is anticipated that further evidence from high-quality trials will inform local licensure and treatment guidelines in the future.
Despite the acceptance of cryoprecipitate for fibrinogen supplementation in acquired coagulopathy in many countries, there remains a lack of Level 1 evidence to support its use. In addition, there is undoubtedly inappropriate administration of cryoprecipitate. As with all allogeneic blood products, cryoprecipitate carries a risk of pathogen transmission and transfusion-associated adverse events.
There is a need for prospective, randomized, controlled clinical trials to determine the haemostatic efficacy of cryoprecipitate compared with the efficacy of alternative preparations.
It is anticipated that these trials will lead to the production of evidence-based guidelines to inform physicians and guide clinical practice.
Editing support was provided by Meridian HealthComms Ltd. Google Scholar. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
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Clinical settings with acquired coagulopathy. Commercial fibrinogen preparations. Current licensing and regulatory status. Dosing strategies. Point-of-care monitoring. Future directions. Declaration of interest. Cryoprecipitate therapy. Nascimento , B. Oxford Academic. E-mail jerrold. Cite Cite B. Select Format Select format. Abstract Cryoprecipitate, originally developed as a therapy for patients with antihaemophilic factor deficiency, or haemophilia A, has been in use for almost 50 yr.
Table 1 Variability between centres of cryoprecipitate pool content and volume. Volume ml. Open in new tab. Table 2 Country-specific guidelines and recommendations for the content and use of cryoprecipitate. Threshold for fibrinogen supplementation. Indication in acquired bleeding. Indication in congenital bleeding. Should not be used if virus-inactivated factor concentrates are available Control of uraemic bleeding only after other modalities have failed Do not use unless results of laboratory studies indicate a specific haemostatic defect for which this product is indicated Indicated as second-line therapy for vWD and haemophilia A.
Coagulation factor preparations other than cryoprecipitate are preferred when blood component therapy is needed for management of vWD and haemophilia A. Cryoprecipitate may be given when a large volume of plasma is contraindicated Cryoprecipitate can be used to manage intracranial bleeding during or post-tPA administration in stroke patients, or other clinical scenarios Cryoprecipitate can be used to treat FXIII deficiency if specific coagulation factor concentrate is not available Cryoprecipitate can be used in vWD unresponsive to DDAVP and in those locations where Factor VIII: C concentrates are not available for haemophilia A patients.
Every effort must be made to obtain the preferred recombinant factor concentrate for haemophiliacs before the use of cryoprecipitate Worldwide World Federation of Hemophilia WFH Guidelines for the management of hemophilia 89 The WFH strongly recommends the use of viral-inactivated plasma-derived or recombinant concentrates in preference to cryoprecipitate for the treatment of haemophilia and other inherited bleeding disorders.
Preparation and properties of serum and plasma proteins; a system for the separation into fractions of the protein and lipoprotein components of biological tissues and fluids.
Google Scholar Crossref. Search ADS. Treatment of classic hemophilia: the use of fibrinogen rich in factor VIII for hemorrhage and for surgery.
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