Clinical indications of FFP

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Clinical indications of FFP

• 4C1 Ri ???

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Part I

• Guidelines for the use of fresh-frozen plasma,
  cryoprecipitate and cryosupernatant
• British Committee for Standards in Haematology,
  Blood Transfusion Task Force (J. Duguid,
  Chairman) D. F. OShaughnessy (Convenor, Task
  Force nominee),1, C. Atterbury (RCN nominee),2
  P. Bolton Maggs (RCPCH nominee),3 M. Murphy (Task
  Force nominee),4 D. Thomas (RCA nominee),5 S.
  Yates (representing Biomedical Scientists)6 and
  L. M. Williamson (Task Force nominee)7

British Journal of Haematology 2004 12611
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Guidelines for FFP

• Single inherited clotting factor deficiencies for
  which no virus-safe fractionated product is
  available. ex. Factor V
• Multi-factor deficiencies associated with severe
  bleeding (ex.DIC with bleeding)
• Fresh-frozen plasma is not indicated in DIC with
  no evidence of bleeding.
• Hypofibrinogenemia Cryoprecipitate may be
  indicated if the plasma fibrinogen is less than 1
  g/l,
• TTP
• Single volume daily plasma exchange should
  ideally be begun at presentation (grade A
  recommendation, level Ib evidence)

British Journal of Haematology 2004 12611
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DIC

• Treating the underlying cause is the cornerstone
  of managing DIC.
• If the patient is bleeding, a combination of FFP,
  platelets and cryoprecipitate is indicated.
• If there is no bleeding, blood products are not
  indicated, whatever the results of the laboratory
  tests, and there is no evidence for prophylaxis
  with platelets or plasma

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Guidelines for FFP

• Reversal of warfarin effect when severe bleeding
  
• Partial effect
• Fresh-frozen plasma should never be used for the
  reversal of warfarin anticoagulation when there
  is no evidence of severe bleeding (grade B
  recommendation, level IIa evidence).
• Vitamin K deficiency in the intensive care unit
  (ICU)
• Fresh-frozen plasma should not be used to correct
  prolonged clotting times in ICU patients
• this should be managed with vitamin K

British Journal of Haematology 2004 12611
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Reversal of warfarin effect

• Warfarin achieves its anticoagulant effect by
  inhibiting the vitamin K-facilitated
  carboxylation of FII, FVII, FIX and FX.
• Withdrawing warfarin, giving vitamin K orally or
  parenterally transfusing FFP, or transfusing PCC
  (FII, FVII, FIX and FX, or separate infusions of
  FII, FIX and FX concentrate and FVII
  concentrate). Prothrombin complex concentrate (50
  units/kg) is preferred to FFP.
• Makris et al (1997) showed that FFP contains
  insufficient concentration of the vitamin K
  factors (especially Factor IX) to reverse
  warfarin, supporting the finding that FFP is not
  the optimal treatment.

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Vitamin K policies in ICUs

• Many patients in ICU have an inadequate vitamin K
  intake, particularly as parenteral nutrition for
  the seriously ill usually has a restricted lipid
  component.
• Intensive care unit patients should routinely
  receive vitamin K
• 10 mg thrice weekly for adults 0-3 mg per kg for
  children (grade B recommendation,level IIa
  evidence).

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Guidelines for FFP

• Liver disease
• Platelet count and function, as well as vascular
  integrity, may be more important in these
  circumstances.
• The response to FFP in liver disease is
  unpredictable. Complete normalization of the
  haemostatic defect does not always occur. If FFP
  is given, coagulation tests should be repeated.
• There is no evidence to substantiate the practice
  in many liver units of undertaking liver biopsy
  only if the PT is within 4 s of the control
  (grade C recommendation, level IV evidence).

British Journal of Haematology 2004 12611
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Guidelines for FFP

• Surgical bleeding
• Should be guided by timely tests of coagulation
• FFP should never be used as a simple volume
  relacement in adults or children (grade B
  recommendation, level IIb evidence).
• Massive transfusion
• If bleeding continues after large volumes of
  crystalloid, red cells and platelets have been
  transfused, FFP and cryoprecipitate may be given
  so that the PT and APTT ratios are shortened to
  within 1.5, and a fibrinogen concentration of at
  least 1.0 g/l in plasma obtained.

British Journal of Haematology 2004 12611
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Guidelines for FFP

• Pediatric use of FFP
• should only receive pathogen-reduced FFP (PRFFP)
• Haemorrhagic disease of the newborn
• FFP 1020 ml/kg IV vitamin K. Prothrombin
  complex concentrate.
• Who are about to undergo an invasive procedure,
  should receive FFP and vitamin K.
• Routine administration of FFP to prevent
  periventricular haemorrhage (PVH) in preterm
  infants is not indicated

British Journal of Haematology 2004 12611
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Adverse effects of FFP

• 1. Allergy resulting in urticaria has been
  reported in 13 of transfusion, whil anaphylaxis
  is rare.
• 2.Transfusion-related acute lung injury
• 0.02 of transfusion.
• Severe respiratory distress, with hypoxia,
  pulmonary edema, infiltrates or white-out on
  chest X-ray, and sometimes fever and hypotension.
• Usually develops within 4 h of transfusion.
• It cannot be distinguished clinically from ARDS.

British Journal of Haematology 2004 12611
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Adverse effects of FFP

• 3. Infection
• The freezing process inactivates bacteria.
  Bacterial contamination and growth, with
  endotoxin production, prior to freezing is
  unlikely, and has not been reported in the UK in
  the past 5 years.
• However, freezing does not remove free viruses
  such as hepatitis A, B and C, human
  immunodeficiency virus (HIV) 1 2, and
  parvovirus B19.
• HIV 1 2 0-1 in 10 million
• hepatitis C 0-2 in 10 million
• hepatitis B 0-3 in 10 million.
• Patients likely to receive multiple units of FFP,
  such as those with a congenital coagulopathy,
  should be considered for vaccination against
  hepatitis A and B.

British Journal of Haematology 2004 12611
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No justification for the use of FFP

• 1. Hypovolemia
• Crystalloids are safer, cheaper and more readily
  available.
• 2. Plasma exchange (except for TTP)
• May results in the progressive reduction of
  coagulation factors, immunoglobulins, complement
  and fibronectin.
• Haemorrhage and/or infections are not
  encountered.
• There may be a problem with pseudocholinesterase
  levels being low as a result of many plasma
  exchanges with saline/albumin if the patient then
  needs an anaesthetic. This can be corrected with
  FFP.
• 3. Prolonged INR in the absence of bleeding.

British Journal of Haematology 2004 12611
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Part II

• Albumin use in resuscitation.
• A Comparison of Albumin and Saline for Fluid
  Resuscitation in the Intensive Care Unit
• NEJM Volume 350, May 2004, pp 2247-2256

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Volume expander?

• A Comparison of Albumin and Saline for Fluid
  Resuscitation in the Intensive Care UnitNEJM
  Volume 3502247-2256. May 27,2004.
• Saline versus Albumin Fluid Evaluation (SAFE)
  Study in 16 ICUs in Australia and New Zealand
• Total N6997, Exculsion Patients admitted to the
  ICU after cardiac surgery, after liver
  transplantation, or for the treatment of burns.
• Double-blind, randomized trial
• Two groups similar baseline characteristics.

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N Engl J Med 2004 3502247
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N Engl J Med 2004 3502247
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Results

• 726 deaths/in 3497 pt 4 albumin
• 729 deaths /in 3500 pt- saline
• In patients in the ICU, use of either 4 percent
  albumin or normal saline for fluid resuscitation
  results in similar outcomes at 28 days.

N Engl J Med 2004 3502247
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N Engl J Med 2004 3502247
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• In our study, patients who were resuscitated with
  albumin received less fluid than those who were
  resuscitated with saline.
• However, there was no significant difference in
  mean arterial pressure between the groups, and
  the differences in central venous pressure and
  heart rate were small.
• Patients who were assigned to albumin received a
  significantly greater volume of PRBC during the
  first two days of the study.
• The reasons for this difference remain
  speculative but may include greater hemodilution
  with albumin than with saline or increased blood
  loss with albumin due to transient alterations in
  coagulation .

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Conclusion

• Albumin and saline should be considered
  clinically equivalent treatments for
  intravascular volume resuscitation in a
  heterogeneous population of patients in the ICU.
• Whether either albumin or saline confers benefit
  in more highly selected populations of critically
  ill patients requires further study.
• 
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• Thanks for your attention !!

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TRALI

• According to some authors, TRALI develops in two
  steps (Silliman et al, 2003).
• First, a predisposing condition
• surgery or active infection.
• -gtcause cytokines releasing and neutrophils
  attaching to the vascular endothelium
  particularly in the pulmonary capillaries.
• The second step
• lipid and other cytokines, or human leucocyte
  antigen or granulocyte alloantibodies (found in
  80 of the donors in some series, most of whom
  are women who have been pregnant)
• -gtcause further neutrophil priming, activation
  and pulmonary damage.

British Journal of Haematology 2004 12611
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Cryosupernatant

• The current established treatment of thrombotic
  thrombocytopenic purpura (TTP) is plasma exchange
  with fresh frozen plasma (FFP). With this
  treatment, there is a 49 response after seven
  exchanges and a 78 survival at 1 month. Although
  the exact cause of TTP is unknown, the presence
  of von Willebrand factor (VWF) multimers has been
  implicated in the disease. Accordingly, it has
  been suggested that cryosupernatant (plasma from
  which cryoprecipitate has been removed), which is
  relatively deficient in VWF multimers, might be
  an effective replacement fluid during plasma
  exchange.
• British Journal of HaematologyVolume 94 Page
  383  - August 1996

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Complications of therapeutic plasma exchange
UpToDate

• Therapeutic plasma exchange (TPE,
  plasmapheresis) is an extracorporeal blood
  purification technique designed for the removal
  of large molecular weight substances from the
  plasma. This topic review will discuss the
  complications associated with this procedure the
  prescription and technique of TPE are discussed
  separately. (See "Prescription and technique of
  therapeutic plasma exchange").
• COMPLICATIONS A review of the reported
  complications from over 15,000 plasma exchange
  treatments found that adverse reactions were
  substantially more common with fresh frozen
  plasma (FFP) than with albumin replacement (20
  versus 1.4 percent) 1. The most frequent
  problems are citrate-induced paresthesias (due to
  binding of free calcium to citrate), muscle
  cramps, and urticaria 2. More serious
  complications, such as severe anaphylactoid
  reactions, typically follow the administration of
  FFP and other plasma-containing replacement fluid
  3. The overall incidence of death is 0.03 to
  0.05 percent (see below) 1,3.

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Complications of therapeutic plasma exchange
UpToDate

• Hypotension TPE can lead to a reduction in
  blood pressure that is usually due to a decrease
  in intravascular volume. A certain proportion of
  whole blood must necessarily be extracorporeal
  during the procedure. With continuous flow
  technology, the extracorporeal volume is usually
  no more than 15 percent of the patient's
  intravascular volume however, instrumentation
  which utilizes discontinuous flow technology may
  have higher extracorporeal volumes. Infusing
  additional intravascular fluid or increasing the
  return rate can return the blood pressure toward
  the baseline level.If a fall blood pressure is
  accompanied by a decrease in pulse rate,
  diaphoresis, and/or syncope, it is likely that a
  vasovagal reaction is occurring. Lowering the
  patient's head, using ammonium salts, and
  stopping the procedure temporarily are the
  appropriate responses to this type of reaction.
• Dyspnea The development of shortness of breath
  or dyspnea suggests the presence of pulmonary
  edema due to fluid overload. Noncardiogenic edema
  can rarely occur and, if the blood components
  being reinfused are not adequately
  anticoagulated, massive pulmonary emboli can
  ensue. The latter is a rare occurrence, since
  state-of-the-art blood cell separators control
  and monitor anticoagulant volumes.