Patrick Mollison CBE. 17 March 1914—26 November 2011

Patrick Mollison was a pioneer in blood transfusion, playing a major role in changing it from a risky procedure to one which is now extremely safe. The urgent need for blood during World War II provided a stimulus for the development of this important lifesaving measure. His first major contribution was to devise a mechanism whereby blood could be stored for more than just short periods. Mixing donated blood with acid–citrate–dextrose (ACD) became a standard procedure for almost 30 years and was used worldwide. He later took a special interest in haemolytic disease of the newborn (HDN), which was largely due to Rhesus incompatibility between mother and baby. He was also involved with work which eventually led to HDN becoming preventable with the use of anti-D treatment of mothers. He wrote the first standard textbook on blood transfusion; almost 70 years later it is in its eleventh edition and still bears his name in the title. He spent his working life in blood transfusion and the study of the scientific aspects of this subject, developing a university department at Hammersmith Hospital and publishing almost 200 scientific papers as well as the textbook. He was very much a clinical scientist rather than a front-line clinician, although he was physician to Her Majesty Queen Elizabeth and was present at the birth of all four of her children.

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Blood and the hidden virus

10.1093/med/9780198717607.003.0005 ◽

2016 ◽

Author(s):

Shaun R. McCann

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Blood Transfusion ◽

Blood Donation ◽

Blood Groups ◽

Blood Products ◽

Haemolytic Disease ◽

History Of ◽

Jakob Disease ◽

Donated Blood

A major achievement in the history of blood transfusion was discovery of the rhesus blood groups. The work of Philip Levine and Rufus Stetson led to the discovery of the Rh factor and its relevance to haemolytic disease of the newborn. Later developments led to the generation of the anti-Rh (anti-D) antibodies. The chapter goes on to discuss the contamination of anti-D blood products with hepatitis C and the subsequent isolation of the hepatitis C virus. The contamination of donated blood products by hepatitis C and variant Creutzfeldt–Jakob disease is discussed, with specific relevance to the practice of blood donation and screening processes.

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Conditions Affecting the Responses of Human Platelets to Epinephrine

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647031 ◽

1988 ◽

Vol 60 (02) ◽

pp. 209-216 ◽

Cited By ~ 23

Author(s):

Chantal Lalau Keraly ◽

Raelene L Kinlough-Rathbone ◽

Marian A Packham ◽

Hidenori Suzuki ◽

J Fraser Mustard

Keyword(s):

Platelet Rich Plasma ◽

Shape Change ◽

Human Platelets ◽

Dense Granule ◽

Primary Phase ◽

Lag Phase ◽

Acid Citrate Dextrose ◽

Two Phases ◽

Citrate Dextrose ◽

Thromboxane Formation

SummaryConditions affecting the responses of human platelets to epinephrine were examined. In platelet-rich plasma prepared from blood anticoagulated with hirudin or PPACK (D-pheny- lalanyl-L-prolyl-L-arginine chloromethyl ketone), epinephrine did not cause shape change or aggregation. In a Tyrode-albumin- apyrase solution containing a concentration of Ca2+ in the physiological range, and fibrinogen, epinephrine in concentrations as high as 40 μM did not induce platelet shape change, caused either no primary aggregation or very slight primary aggregation, and did not induce thromboxane formation, release of dense granule contents, or secondary aggregation. In contrast, in citrated platelet-rich plasma, epinephrine induced two phases of aggregation. This is not attributable to the generation of traces of thrombin since the same effects were evident when blood was taken into a combined citrate-hirudin anticoagulant or a combined citrate-PPACK anticoagulant. In a modified Tyrode-albu- min-apyrase solution containing approximately 20 μM Ca2+, 1 mM Mg2+, and fibrinogen, epinephrine induced extensive aggregation after a lag phase, but no primary phase was evident; thromboxane formation and release of dense granule contents accompanied the aggregation response. These responses were also observed when PPACK was included with the acid-citrate- dextrose anticoagulant, and in the washing and resuspending fluids. In the presence of aspirin or the thromboxane receptor blocker BM 13.177 a few small aggregates were detected by particle counting and by scanning electron microscopy; with the latter inhibitor, the platelets in the aggregates retained their disc shape; secondary aggregation and the responses associated with it did not occur. Thus thromboxane A2 formation is not necessary for the formation of these small aggregates, but is required for extensive aggregation and release. As with other weak agonists, the close platelet-to-platelet contact in the low Ca2+ medium appears to be necessary for full secondary aggregation. Omission of fibrinogen from the low Ca2+ medium prevented both primary and secondary aggregation in response to epinephrine. An antibody (10E5) to the glycoprotein Ilb/IIIa complex was completely inhibitory in the presence of fibrinogen. Thus the response of human platelets to epinephrine is influenced by the concentration of Ca2+ and the presence of fibrinogen in the medium in which they are suspended.

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RISTOMYCIN (AGGRISTIN) PRECIPITATION TEST: A NEW, RAPID AND RELIABLE METHOD FOR THE DETECTION OF INTRAVASCULAR CLOTTING

10.1055/s-0038-1643133 ◽

1987 ◽

Author(s):

G Pfliegler ◽

J Arnout ◽

J Vermylen

Keyword(s):

Reliable Method ◽

Degradation Products ◽

Laboratory Diagnosis ◽

Blood Collection ◽

Vein Thrombosis ◽

Fibrin Degradation Products ◽

Acid Citrate Dextrose ◽

Citrate Dextrose ◽

Precipitation Test

The rapid and specific detection of fibrin monomers (fm) and fibrin degradation products (fdp) is of major importance in the laboratory diagnosis of disseminated intravascular coagulation, deep vein thrombosis or pulmonary embolism. Most methods in use are either time-consuming, needing special techniques, or insensitive and poorly specific. Some time ago, Watanabe and Tullis described a simple and rapid, semiquantitative test to detect fm and fdp in plasma, based on the finding that ristocetin in low concentrations (1.0-1.5 mg/ml) can specifically precipitate fm and fdp. To 0.4 ml ACD plasma, 0.1 ml ristocetin (2.5 mg/ml) is added and vortexed. The mixture is then incubated for 30 min at 20°C and centrifuged at 50xg for 5 min. The test is considered to be positive when fibrin-like strands or small or large pellets are observed on the bottom of the tube. More recently, Pfliegler et al. reported that ristomycin (AGGRISTIN), a structural analogue of ristocetin, can replace ristocetin in this test.Here we report on further results with the ristomycin (AGGRISTIN) precipitation test in 138 patients with various intravascular thrombotic events. The results of this test, performed on ACD plasma, were compared to the serum fdp values detected by immunoelectrophoresis (IEF) and by the haemagglutina-tion inhibition test (HIT). In all 30 cases with serum fdp above 30 ug/ml (HIT) or 28 pg/ml (IEF), the precipitation test was positive; at lower fdp concentrations, as detected by HIT or IEF, the test still was positive in 70 per cent of these thrombosis patients, suggesting a superior sensitivity. In 16 patients with elevated fibrinogen levels (but no evidence of thrombosis), the test was positive in only 3. No false positive results were detected in 16 healthy controls. Preliminary results show that the minor disadvantage of the test (blood collection on acid citrate dextrose) may readily be overcome by the in vitro adjustment of the pH of citrate plasma, commonly used for other haemostatic tests, to between 7.0 and 7.4.On the basis of our results we suggest that the AGGRISTIN (ristomycin) precipitation test is a simple, rapid and reliable method for the laboratory diagnosis of intravascular clotting.

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Acute Isovolaemic Haemodilution: The Best Option for Autologous Blood Transfusion in Africa?

Tropical Doctor ◽

10.1177/004947559502500403 ◽

1995 ◽

Vol 25 (4) ◽

pp. 152-155 ◽

Cited By ~ 1

Author(s):

Zacharia A Berege ◽

Bart Jacobs ◽

Michael R Matasha ◽

Frank Mpelumbe ◽

Ernestini Kimaro

Keyword(s):

Blood Transfusion ◽

Blood Loss ◽

Autologous Blood ◽

Autologous Blood Transfusion ◽

Total Blood Volume ◽

East African ◽

Homologous Blood ◽

Total Blood ◽

Induction Of Anaesthesia ◽

Donated Blood

The purpose of this study was to identify the best method of autologous blood transfusion to be applied in an East African hospital. One hundred and nine consecutive patients for whom major blood loss was anticipated were enrolled. Seventeen patients donated 1 unit of blood 3 days preoperatively and 92 underwent acute isovolaemic haemodilution prior to induction of anaesthesia. For the haemodiluted patients a 2:1 ratio of sterile pryogen-free saline to collected blood was used. One of the 16 patients from whom 2 units were withdrawn by haemodilution experienced hypovolaemia which was rapidly restored by additional transfusion of colloid. Of the patients who donated blood preoperatively only 23.5% were autotransfused compared to 98.9% of the haemodiluted patients. Of the latter 23.9% (22) had an intraoperative blood loss exceeding 15% of their total blood volume and 7.6% (7) lost more than 25%. Only one received homologous blood in addition. For hospitals with limited blood bank facilities and regular cancellation of surgery, the use of acute isovolaemic haemodilution is recommended. A 3:1 ratio of saline to blood is now advised when 1 unit is withdrawn and a part replacement with crystalloid when 2 units are collected.

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Implementation of a Simplified Regional Citrate Anticoagulation Protocol for Post-Dilution Continuous Hemofiltration Using a Bicarbonate Buffered, Calcium Containing Replacement Solution

Blood Purification ◽

10.1159/000452755 ◽

2016 ◽

Vol 42 (4) ◽

pp. 349-355 ◽

Cited By ~ 6

Author(s):

Christopher J. Kirwan ◽

Ross Hutchison ◽

Sherif Ghabina ◽

Stephanie Schwarze ◽

Abigail Beane ◽

...

Keyword(s):

Metabolic Alkalosis ◽

Calcium Supplementation ◽

Regional Citrate Anticoagulation ◽

Prospective Audit ◽

Bleeding Events ◽

Continuous Hemofiltration ◽

Citrate Anticoagulation ◽

Replacement Solution ◽

Acid Citrate Dextrose ◽

Citrate Dextrose

Background/Aims: Recent updates to the Nikkiso Aquarius continuous renal replacement therapy (CRRT) platform allowed us to develop a post-dilution protocol for regional citrate anticoagulation (RCA) using standard bicarbonate buffered, calcium containing replacement solution with acid citrate dextrose formula-A as a citrate source. Our objective was to demonstrate that the protocol was safe and effective. Methods: Prospective audit of consecutive patients receiving RCA for CRRT within intensive care unit, who were either contraindicated to heparin or had poor filter lifespan (<12 h for 2 consecutive filters) on heparin. Results: We present the first 29 patients who used 98 filters. After excluding ‘non-clot' filter loss, 50% had a duration of >27 h. Calcium supplementation was required for 30 (30%) filter circuits, in 17 of 29 (58%) patients. One patient discontinued the treatment due to metabolic alkalosis, but there were no adverse bleeding events. Conclusion: Post-dilution RCA system is effective and simple to use on the Aquarius platform and results in comparable filter life for patients relatively contraindicated to heparin.

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Regional anticoagulation with acid citrate dextrose-A for extracorporeal photoimmunochemotherapy

Vox Sanguinis ◽

10.1046/j.1423-0410.2002.00213.x ◽

2002 ◽

Vol 83 (3) ◽

pp. 222-226 ◽

Cited By ~ 7

Author(s):

R. Apsner ◽

B. Uenver ◽

G. Sunder-Plassmann ◽

R. M. Knobler

Keyword(s):

Acid Citrate Dextrose ◽

Citrate Dextrose ◽

Regional Anticoagulation

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Intracellular pH (pHi) of Red Cells Stored in Acid Citrate Dextrose Medium

The Journal of Biochemistry ◽

10.1093/oxfordjournals.jbchem.a130929 ◽

1975 ◽

Vol 78 (3) ◽

pp. 469-474 ◽

Cited By ~ 3

Author(s):

Sachiko TSUDA ◽

Akio TOMODA ◽

Shigeki MINAKAMI

Keyword(s):

Intracellular Ph ◽

Red Cells ◽

Acid Citrate Dextrose ◽

Citrate Dextrose

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Preparation of optically clear lyophilized human serum for use in preparing control material.

Clinical Chemistry ◽

10.1093/clinchem/22.4.456 ◽

1976 ◽

Vol 22 (4) ◽

pp. 456-460 ◽

Cited By ~ 11

Author(s):

G J Proksch ◽

D P Bonderman

Keyword(s):

Human Serum ◽

Dextran Sulfate ◽

Raw Materials ◽

Divalent Metal ◽

Divalent Metal Ions ◽

Quality Control Material ◽

Control Material ◽

Acid Citrate Dextrose ◽

Citrate Dextrose ◽

Citrate Phosphate

Abstract We describe a simple, rapid process--which includes the specific precipitation of pre-beta and beta-lipoproteins with dextran sulfate and divalent metal ions--for preparing an optically clear human serum that retains its clarity upon reconstitution with water after having been frozen and lyophilized. Such serum contains the normal constituents of human serum, except for the removed lipoproteins. The process causes no apparent interference with results of analyses for 22 of the more commonly measured constituents. Fresh or aged pooled serum or blood-bank plasma containing acid-citrate-dextrose or citrate-phosphate-dextrose are equally suitable as raw materials. This stabilized serum is an excellent matrix for use in preparing standards and quality-control material for assay of components of human serum.

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