Plasma

(USAN, rINN)

💊 Chemical information

stinguendum Virum). A frozen or freeze-dried, sterile, non-pyrogenic preparation obtained from human plasma derived from donors belonging to the same ABO blood group. The plasma used complies with the requirements for Human Plasma for Fractionation (above). The method of preparation is designed to minimise activation of any coagulation factor and includes a step or steps that have been shown to inactivate known agents of infection. The frozen preparation, after thawing, is a clear or slightly opalescent liquid free from solid and gelatinous particles. The freezedried preparation is an almost white or slightly yellow powder or friable solid.

💊 Adverse Effects and Precautions

As for Blood, though with a low risk of transmitting cell-associated viruses. However, the production of blood products using plasma from UK donors has been phased out due to the possible risk of transmission of Creutzfeldt-Jakob disease.

💊 Uses and Administration

Fresh frozen plasma contains useful amounts of clotting factors. It should be reserved for patients with proven abnormalities in blood coagulation. Indications include congenital deficiencies in clotting factors for which specific concentrates are unavailable, severe multiple clotting factor deficiencies (for example in patients with liver disease), rapid reversal of the action of coumarin anticoagulants, and disseminated intravascular coagulation. It may be used after massive blood transfusion when there is evidence of coagulation deficiency but its value for routine prophylaxis against abnormal bleeding tendencies in patients receiving massive blood transfusions is contentious except where clotting abnormalities have been confirmed. It has also been used in the treatment of thrombotic thrombocytopenic purpura and as a source of plasma proteins. The amount of fresh frozen plasma transfused depends on the required level of clotting factors. A unit of fresh frozen plasma refers to the quantity of plasma obtained from 1 unit of whole blood; this generally represents a volume of about 250 mL, including anticoagulant. Fresh frozen plasma should not be used as a volume expander or as a nutritional source. Therapeutic plasma exchange or plasmapheresis (see below) are used in a wide variety of disorders. Plasma is used to prepare blood products including albumin, antithrombin III, blood clotting factors, immunoglobulins, and platelets. Other preparations include cryoprecipitate depleted plasma, which is deficient in fibrinogen, factor VIII, von Willebrand factor, cryoglobulin, and fibronectin, and single donor plasma, which is not frozen. A solvent-detergent-treated plasma preparation is available.

Guidelines and reviews.

General references to the use of plasma.
1. Fresh-frozen Plasma, Cryoprecipitate, and Platelets Administration Practice Guidelines Development Task Force of the College of American Pathologists. Practice parameter for the use of fresh-frozen plasma, cryoprecipitate, and platelets. JAMA 1994; 271: 777–81
2. Cohen H, et al. Plasma, plasma products, and indications for their use. In: Contreras M, ed. ABC of transfusion. 3rd ed. London; BMJ Books, 1998: 40–44
3. British Committee for Standards in Haematology, Blood Transfusion Task Force. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol 2004; 126: 11–28. Also available at: http://www.bcshguidelines.com/pdf/ freshfrozen_280604.pdf (accessed 27/10/05) Addenda, amendments, and corrections (4 sets) at http://www.bcshguidelines.com/ pdf/Amendments_FFP_091205.pdf (issued 07/12/05), ibid. 2007; 136: 514–16, at http://www.bcshguidelines.com/pdf/ FFPAmendment_1_17_Oct_2007.pdf (issued 17/10/07), at http://www.bcshguidelines.com/pdf/FFPAmendment_2_17_Oct_ 2007.pdf (issued 17/10/07) (accessed 19/06/08
4. Stanworth SJ, et al. Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials. Br J Haematol 2004; 126: 139–52.

Hereditary angioedema.

For a mention of fresh frozen plasma being used in hereditary angioedema.

Neonatal intraventricular haemorrhage.

Plasma volume expansion in preterm neonates has been thought to help prevent neonatal intraventricular haemorrhage. However, a study using plasma or gelatin as plasma volume expanders,1,2found no evidence of a decreased risk of such haemorrhage or subsequent death or disability.
1. The Northern Neonatal Nursing Initiative Trial Group. A randomized trial comparing the effect of prophylactic intravenous fresh frozen plasma, gelatin or glucose on early mortality and morbidity in preterm babies. Eur J Pediatr 1996; 155: 580–8
2. Northern Neonatal Nursing Initiative Trial Group. Randomised trial of prophylactic early fresh-frozen plasma or gelatin or glucose in preterm babies: outcome at 2 years. Lancet 1996; 348: 229–32.

Plasma exchange.

Therapeutic plasma exchange or plasmapheresis are procedures in which plasma is selectively removed from the body while the cellular constituents of blood are retained. Although the two terms are commonly used synonymously, plasmapheresis generally involves the removal of small volumes of plasma, whereas plasma exchange removes larger volumes which must be replaced with a suitable fluid. They have been tried in a number of disorders, including many with an immunological basis, when conventional treatment has not been successful. The aim is removal or reduction of those constituents of plasma causing or aggravating a disease or replacement of deficient plasma factors if the deficiency is the cause of the disorder. Volume and frequency of plasma exchange is determined by the pathophysiology of the undesirable plasma constituent. For example, removal of antibody usually requires exchange of 1.5 times the estimated plasma volume (3 to 4 litres) repeated daily or on alternate days until the desired reduction is obtained. The replacement fluid used depends on the volume and the condition being treated; albumin solutions, plasma expanders, or sodium chloride 0.9% are frequently used, whereas in conditions where there is deficiency of a plasma factor replacement of blood components such as immunoglobulins may be required. Fresh frozen plasma has been used as a replacement fluid but is associated with a high incidence of adverse effects and is generally reserved for the management of thrombotic thrombocytopenic purpura. Technological developments, such as the use of specific adsorbents and the use of multiple filters with different pore sizes, may enable removal of only the desired constituent and avoid removal and subsequent replacement of total plasma.
1. Urbaniak SJ, Robinson EA. Therapeutic apheresis. In: Contreras M, ed. ABC of transfusion. 3rd ed. London: BMJ Books, 1998: 67–70
2. Michaud D, et al. Therapeutic plasma exchange. Dynamics 2001; 12: 18–24
3. Madore F. Plasmapheresis: technical aspects and indications. Crit Care Clin 2002; 18: 375–92
4. McLeod BC. Therapeutic apheresis: use of human serum albumin, fresh frozen plasma and cryosupernatant plasma in therapeutic plasma exchange. Best Pract Res Clin Haematol 2006; 19: 157–67.

Thrombotic microangiopathies.

Thrombotic thrombocytopenic purpura and haemolytic-uraemic syndrome are both syndromes characterised by intravascular platelet clumping.1-6Thrombocytopenia also occurs and fragmentation of erythrocytes, partly caused by the red cells passing through areas of the microvasculature occluded by the platelet aggregation, leads to microvascular haemolytic anaemia. In thrombotic thrombocytopenic purpura (TTP) the platelet aggregation is extensive and obstructs the vessels of various organs producing ischaemia or even infarction. The CNS, notably the brain, is often the area predominantly affected although some degree of renal involvement may occur. It is an uncommon disorder; adult women, in whom the condition presents as a chronic relapsing illness, are slightly more frequently affected. It may be associated with abnormalities of von Willebrand factor due to deficiency or impaired activity of a protease, ADAMTS-13.5,6 In haemolytic-uraemic syndrome (HUS) the platelet aggregation is relatively less widespread and less severe and mainly affects the renal microvasculature although extra-renal manifestations may also occur. The primary consequences are hypertension and acute renal insufficiency or ultimately, if untreated, renal failure. Most cases of HUS occur in early childhood and follow a diarrhoeal illness caused by Shigella dysenteriae or Escherichia coli. However, the condition is becoming increasingly recognised in adults, particularly the elderly. Some cases may be drug induced. With appropriate symptomatic therapy HUS is typically a self-limiting disease with spontaneous recovery although fatalities have been known. The supportive management of both syndromes follows similar lines.1,3,4 In HUS, or TTP with renal symptoms, special attention needs to be directed towards the prevention of renal failure. Hypovolaemia should be corrected, with careful control of fluid and electrolyte balance and hypertension. Haemodialysis will be needed if renal failure develops. Severe anaemia requires blood transfusion, but platelet transfusion should be avoided. Plasma exchange (see above) is considered to be the mainstay of therapy for TTP.1-6 The optimal regimen has not been determined, but it is usually performed daily. There is also some debate about the preferred fluid replacement; plasma exchange using cryosupernatant (the plasma remaining after cryoprecipitate is prepared, and which is depleted of von Willebrand factor) may be more efficacious than fresh frozen plasma.3 When plasma exchange is not available, infusion of fresh frozen plasma may be used.1,3 In HUS, there is some debate over the use of plasma exchange or infusion. Some consider that these have no proven benefit in HUS2,3 but others1 have challenged this belief. Antiplatelet therapy and corticosteroids are often given, although neither has been adequately investigated and antiplatelets such as ticlopidine and clopidogrel have been reported to cause TTP. Aspirin and dipyridamole have been used, but are not recommended when profound thrombocytopenia is present because of the potential bleeding risk, without proven benefit. However, low-dose aspirin may be used when platelet counts have recovered after plasma exchange in TTP.1,3 Some reports have described improved outcome in both syndromes with corticosteroids.7 They are often used with plasma exchange in TTP.1,3,4 However, a randomised, double-blind trial8 in children with HUS failed to show any difference between oral corticosteroids and placebo in terms of haematological or neurological recovery, although renal function appeared to improve more rapidly in those receiving corticosteroids. Other drugs may also be tried, particularly in refractory TTP. Some treatments that have been reported to be beneficial in case reports or small series include normal immunoglobulin,1,4 azathioprine,1 ciclosporin,1,3 cyclophosphamide,3 and vincristine.1-4The monoclonal antibody, rituximab, is under investigation.2The use of a protein-A immuno-adsorption column may be considered in the management of TTP associated with malignancy or bone marrow transplantation.3 Epoprostenol may be tried in order to inhibit platelet-endothelial interactions but again has not been subject to controlled studies; anecdotal evidence presents both favourable and negative results.9 Alteplase has been used successfully in one patient with HUS.10 Splenectomy may also be considered.1,3,4
1. Elliott MA, Nichols WL. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Mayo Clin Proc 2001; 76: 1154–62
2. Moake JL. Thrombotic microangiopathies. N Engl J Med 2002; 347: 589–600
3. British Society for Haematology. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol 2003; 120: 556–73. Also available at: http://www.bcshguidelines.com/pdf/BJH556.pdf (accessed 27/10/05
4. Nabhan C, Kwaan HC. Current concepts in the diagnosis and management of thrombotic thrombocytopenic purpura. Hematol Oncol Clin North Am 2003; 17: 177–99
5. Mayer SA, Aledort LM. Thrombotic microangiopathy: differential diagnosis, pathophysiology and therapeutic strategies. Mt Sinai J Med 2005; 72: 166–75
6. George JN. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354: 1927–35
7. Bell WR, et al. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: clinical experience in 108 patients. N Engl J Med 1991; 325: 398–403
8. Perez N, et al. Steroids in the hemolytic uremic syndrome. Pediatr Nephrol 1998; 12: 101–4
9. Bobbio-Pallavicini E, et al. Intravenous prostacyclin (as epoprostenol) infusion in thrombotic thrombocytopenic purpura: four case reports and review of the literature. Haematologica 1994; 79: 429–37
10. Kruez W, et al. Successful treatment of haemolytic-uraemic syndrome with recombinant tissue-type plasminogen activator. Lancet 1993; 341: 1665–6.

💊 Preparations

Proprietary Preparations

Austria: Octaplas; Cz.: Octaplas; Fin.: Octaplas; Ger.: Octaplas; Ital.: Octaplas; Plasmasafe; Mex.: Octaplas; Neth.: Octaplas; Norw.: Octaplas; NZ: Octaplas; Port.: Novoplas; Octaplas; Swed.: Octaplas; Switz.: Octaplas; UK: Octaplas. Multi-ingredient: Port.: Quixil.
Published December 16, 2018.