Mabel Adams

Yes, it did change.  I cannot remember when.  It made a huge difference for us.

I have no supporting references but for me, common sense dictates that in a space that small you could not get the probes far enough apart to get any significant temperature variations.  Having said that, regulations, requirements or other such problems seldom involve anything resembling common sense.  Much like common courtesy, common sense is seldom common.
 

Here's one paper that involves extended cold storage of room temperature platelets.  They actually seemed more functional.
Xu F, Gelderman MP, Farrell J, Vostal JG. Temperature cycling improves in vivo recovery of cold-stored human platelets in a mouse model of transfusion. Transfusion. 2013 Jun;53(6):1178-86. doi: 10.1111/j.1537-2995.2012.03896.x. Epub 2012 Sep 24. PMID: 22998069.
 
 
Background: Platelet (PLT) storage at room temperature (RT) is limited to 5 days to prevent growth of bacteria, if present, to high levels. Storage in cold temperatures would reduce bacterial proliferation, but cold-exposed PLTs are rapidly cleared from circulation by the hepatic Ashwell-Morell (AM) receptor, which recognizes PLT surface carbohydrates terminated by β-galactose. We cycled storage temperature between 4 and 37°C to preserve PLT function and reduce bacterial growth.
Study design and methods: Temperature-cycled (TC) human PLTs were stored at 4°C for 12 hours and then incubated at 37°C for 30 minutes before returning back to cold storage. PLTs stored at RT or at 4°C (COLD) or TC for 2, 5, and 7 days were infused into SCID mice and the in vivo recovery was determined at 5, 20, and 60 minutes after transfusion.
Results: PLTs stored for 2 days in COLD had significantly lower in vivo recoveries than RT PLTs. TC PLTs had improved recoveries over COLD and comparable to RT PLTs. After 5- and 7-day storage, TC PLTs had better recoveries than RT and COLD PLTs. PLT surface β-galactose was increased significantly for both COLD and TC PLTs compared to RT. Blocking of the AM receptor by asialofetuin increased COLD but not TC PLT recovery.
Conclusion: TC cold storage may be an effective method to store PLTs without loss of in vivo recovery. The increased β-galactose exposure in TC PLTs suggests that mechanisms in addition to AM receptors may mediate clearance of cold-stored PLTs.

There is a CAP proficiency code "VES" (viscoelastic testing) for TEG and ROTEM testing.

This is what we have from CAP for proficiency:

To a VERY large extent I agree with you, if for no other reason than, it is NOT for laboratory workers to decide on the way a patient is treated (including monitoring during pregnancy).  That having been said, no medical director can be expected to be an expert in ALL aspects of medicine, including pregnancy and foetal medicine, and so a good medical director should be prepared to take advice from world famous scientists, such as the late Prof Dave Anstee, and the very much alive Dr Geoff Daniels.

This is from our ABID SOP (sorry the format is weird): 
a.    Warm Autoantibody Guidelines –(Expert judgment is required on a case-by-case basis to supplement these guidelines.  Contact supervisor or Reference Lab for advice) [return to top]
                        i.        Clues it’s a Warm Auto
1.    Reacts with most or all cells tested—usually at a fairly consistent strength.
2.    Positive DAT.
3.    If it is severe enough that there is hemolytic anemia, the patient would be anemic with a high LDH or bilirubin and high reticulocyte count.  The patient’s plasma sample may appear hemolyzed or icteric.  Haptoglobin would be low.
4.    Contact Blood Bank Supervisor for further consult if uncertain. 
5.    Patient has not taken anti-CD38 (daratumumab/Darzalex/DARA) or anti-CD47 drugs in prior 6 months.
                      ii.        Clues it’s NOT a Warm Auto
1.    Reactivity with most or all cells in gel, usually 2+ or less, varying strength could be HTLA-like antibody or antibody to gel diluent. It’s not uncommon for patients to have a positive DAT without having a detectable warm auto antibody so the positive DAT could be present coincidentally.
a.    To confirm antibody to gel diluent, convert 3% screen cells to 0.8% to run in gel. If negative, turn out the 3-cell gel screen and document situation in the patient record.
b.    An HLTA-like antibody will usually remain detectable (although sometimes weaker) in PEG and even saline techniques.
2.    Alloantibodies:
a.    If patient transfused in the prior 3 months, confer with the most expert person available before calling it a warm-auto.
b.    Elution may produce both a panagglutinin and another specificity or may show only a new alloantibody. The panagglutinin may be so strong a weak allo is undetectable.
c.    If the DAT looks mixed field (repeat IgG DAT in gel for clear-cut mixed field), it may be an allo.
3.    Drug-induced antibody:
a.    Research patient’s diagnoses for multiple myeloma, amyloidosis, or other autoimmune diseases. Look for recent surgeries or infections as a clue for cephalosporin treatment. Research their drug history for cephalosporins and anti-CD38 or anti-CD47 drugs.  There is variability whether these present with only a positive DAT (more common with cephalosporins) or with a negative DAT and positive screen or with both positive.
b.    Rarely, other drugs cause what looks like a warm autoantibody.
                     iii.        When the Auto control (AC) or DAT is positive, first check transfusion history.  The AC could be positive due to a delayed serologic/hemolytic transfusion reaction and NOT a warm auto.  See Positive autocontrol.
                     iv.        If not already done, perform a DAT (Direct Antiglobulin Test Procedure).  Warm autoantibody patients can have RBCs coated with IgG only or IgG and complement both.  Occasionally, only complement may be present.
                      v.        If not already done, perform an antibody panel in gel (or other primary testing method).
                     vi.        People who make warm autoantibodies are more likely to make allo-antibodies as well. We need to identify any allo-antibodies in the sample so we want to avoid detecting the autoantibody if possible but still be able to detect allo-antibodies (at least strong ones).
                    vii.        If reactivity in gel is < 1+ or there are some negative reactions, start a 3% tube PEG antibody screen.  If reactivity in gel is ≥ 1+, start a 3% Saline (no enhancement) 30-minute tube antibody screen.  If amount of specimen is minimal, skip PEG screen and only do saline or, if some negatives, rule out with negative reactions found in gel and run selected cells needed to complete ruling out the usual antibody specificities.
                   viii.        If patient has not been recently transfused and usual specificities can’t be ruled out in tube testing, a PEG Autoadsorption should be considered.  PEG adsorptions should not be attempted with patients who have a strong complement coating.
                     ix.        If can’t rule out usual specificities in tube testing and the patient has been transfused in the past 3 months, send the specimen to the Reference Lab for allo-adsorptions to determine the presence/absence of underlying alloantibodies. See Red Cross (ARC) BloodHub/Connect--Standard Work.  If the patient is too critical to wait for the workup, contact the on-call Pathologist and Blood Bank supervisor.  Phenotypically matched units may be indicated. See Increased Risk Transfusion Release Form. 
                      x.        Turn out ABID results as Warm Autoantibody plus any other specificities detected.
                     xi.        Approach to crossmatching in the presence of warm auto-antibodies:
Situation
Pt Hemolyzing*
XM Methods
XM Results
Enough negs in gel to rule out all usual Ab specificities
Yes
Gel
Incompatible
Enough negs in gel to rule out all usual Ab specificities
No
Gel
Compatible
Can rule out all usual Ab specificities in PEG
Yes
Gel
Incompatible
Can rule out all usual Ab specificities in PEG
No
PEG
Compatible
Can rule out all usual Ab specificities in Saline
Yes
Gel
Incompatible
Can rule out all usual Ab specificities in Saline
No
Saline
Compatible
Alloantibodies identified or can’t rule out some Ab specificities in Saline
Yes
Saline** to assess compatibility with allos, then gel to turn out results
Incompatible
Alloantibodies identified or can’t rule out some Ab specificities in Saline
No
Saline
Compatible
Autoadsorption required and able to rule out usual Ab specificities
Yes or No
Gel with neat plasma
Incompatible
Autoadsorption required and alloantibodies identified or can’t rule out usual Ab specificities
Yes or No
With adsorbed sample** to assess compatibility with allos, then gel with neat sample to turn out results
Incompatible
 
*If patient is hemolyzing, no transfused unit will be truly compatible. Use “incompatible” XM result code in STTx, not “least incompatible” for these cases.
**If second XM method (that’s not to be turned out) is required, record on log sheet.
1.    Warm Auto Notes:
a.    The purpose of the PEG or Saline Antibody screen or PEG adsorption is not to be able to call the primary antibody screen negative, but to rule out underlying alloantibodies.  Generally, these tube ABSC’s will NOT be reported in STTx.
b.    Incubation in the presence of enhancement (gel/PEG) reagents may cause reactivity in the AC that is only an in vitro phenomenon. If the DAT is negative and the AC is positive, antibodies to enhancement constituent or autoantibodies reactive only in enhancement medium should be considered.  An Antibody Elution (Eluate) may help determine the presence/absence of warm autoantibody reactivity.
c.    If the patient is demonstrating active hemolysis, use gel or PEG to crossmatch units. The units still may suffer shortened red cell survival in vivo so calling them incompatible is justifiable.
d.    Consult with Blood Bank Supervisor about performing a full phenotype with the available monoclonal (non-AHG) antisera.  Consider giving phenotypically similar RBCs for transfusion.  If alloantibodies are ruled out in a current specimen, units that are only historically antigen-negative are acceptable.   If we must transfuse before alloantibodies can be ruled out, confirmed antigen-matched units are advised if time permits.
e.    Warm autoantibodies can be confirmed in one of two ways: demonstrate that EGA-treated (antibody removed) pre-transfusion autologous cells react with neat plasma or prove that the antibody reactivity is adsorbed out with pre-transfusion, autologous cells.
f.     Patients on daratumumab (Darzalex or DARA or other anti-cd38 drugs) may appear to have a warm auto antibody but it is actually the drug reacting with the cd38 antigens on the red cells. They may have either a negative or positive DAT and AC.  The only effective way to test these patients is to test against DTT treated cells, recognizing that this will miss antibodies to antigens destroyed by DTT like the Kell system.  These patients benefit from having a pre-treatment antibody screen run and possibly antigen typing for K (and if K positive, for k).  In most cases molecular genotyping may be indicated. See Dithiothreitol (DTT) Treatment and Anti-CD38 Drugs (daratumumab/Darzalex)--Blood Bank Testing.
g.    Additional anti-CD38 drug therapeutics are in clinical trials in addition to Daratumumab (Janssen Biotech) include MOR202 (MorphoSys), Sarclisa -Isatuximab (Sanofi-Aventis), and TAK-079 (Takeda) for treatment of systemic lupus erythematosus, Amyloidosis, or other autoimmune diseases. Daratumumab and Sarclisa are approved for treating multiple myeloma.
h.    CD47 is a glycoprotein expressed on all cells including RBCs and platelets, which usually signals to prevent phagocytosis.  Anti-CD47 blocks this signal targeting cells for destruction. Samples from patients taking anti-CD47 drugs (Hu5F9-G4 or avelumab) will react with everything like a warm auto and the reverse type may be affected like a cold auto. Anti-CD47 interferes with all RBC and platelet serological tests performed including ABO reverse typing. False positive reactions can be seen in all phases of testing (immediate spin, 37°C, and IAT) and with all forms of IAT testing (i.e., tube, gel, solid phase). Reactions with D negative cells may be stronger than with other Rh phenotypes. False negative phenotyping test results can occur due to RBCs heavily coated by anti-CD47. DATs may be falsely negative due to a “blocking effect” caused by high levels of antibody present, but eluates are strongly positive. Plasma interference and strong panreactive eluates are observed as soon as 1 hour after drug infusion. CD47 antigens cannot be denatured with DDT or other common denaturing agents.  It is highly recommended to perform pretransfusion testing, including blood type, antibody screen and extended phenotype (either serological or predictive genotype) before initiating treatment. Using monoclonal Gamma-clone Anti-IgG in indirect antiglobulin testing (which does not detect IgG4 immune classes like anti-CD47) may avoid most of the interference in AHG testing.  Giving antigen-matched units may be an option if full phenotyping is available.  [return to top]
i.      Additional CD47 drug therapies are also in clinical trials and include the CD47 targeting antibodies CC9002 (Celgene), which, like Hu5F9, is also an IgG4 antibody, and the human monoclonal SRF231 (Surface Oncology). CD47 agonists are also in clinical trials. These include TT1-621 (Trillium)31 and ALX148 (ALX Oncology), which are fusion proteins with the Fc region of IgG1 antibody fused to the CD47-binding domain of SIRPα with the goal of interrupting the CD47-SIRPα survival signal. Unlike CD47-targeting antibodies, TT1-621 appears to bind only minimally to human RBCs and interference in pretransfusion testing has not been observed or reported to date.

Thanks for your input.  I was hoping you might respond.
The Daniels book says that "No case of HDFN caused by anti-Lua or -Lub and requiring any treatment other than phototherapy is reported, although raised bilirubin or a positive DAT may be detected."  Does this description equal "clinical significant HDFN" by your definition or is there newer information on more severe HDFN from these since Daniels published the 3rd edition?  My thought is that, if there is no evidence of any case needing any early intervention, then there is no point in running titers to determine when to begin early intervention.
 

Thanks for your input.  I was hoping you might respond.
The Daniels book says that "No case of HDFN caused by anti-Lua or -Lub and requiring any treatment other than phototherapy is reported, although raised bilirubin or a positive DAT may be detected."  Does this description equal "clinical significant HDFN" by your definition or is there newer information on more severe HDFN from these since Daniels published the 3rd edition?  My thought is that, if there is no evidence of any case needing any early intervention, then there is no point in running titers to determine when to begin early intervention.
 

Thanks for your input.  I was hoping you might respond.
The Daniels book says that "No case of HDFN caused by anti-Lua or -Lub and requiring any treatment other than phototherapy is reported, although raised bilirubin or a positive DAT may be detected."  Does this description equal "clinical significant HDFN" by your definition or is there newer information on more severe HDFN from these since Daniels published the 3rd edition?  My thought is that, if there is no evidence of any case needing any early intervention, then there is no point in running titers to determine when to begin early intervention.
 

The fact is that we have little to no evidence that platelet transfusion of any sort will mitigate post-pump bleeding.  This is expert opinion only that has driven this practice. What we have learned in the last few years is that platelet transfusion as currently practiced (ignoring ABO for one thing) actually increases bleeding and mortality in some clinical settings.  I'd rather have some oozing than be transfused with platelets empirically, both as a patient and a hematologist.  With life threatening bleeding and abnormal platelet function as measured by a closure time or TEG/ROTEM, platelet transfusion makes sense and has some data driven support.  Oozing, no data whatever.

Thanks for your input.  I was hoping you might respond.
The Daniels book says that "No case of HDFN caused by anti-Lua or -Lub and requiring any treatment other than phototherapy is reported, although raised bilirubin or a positive DAT may be detected."  Does this description equal "clinical significant HDFN" by your definition or is there newer information on more severe HDFN from these since Daniels published the 3rd edition?  My thought is that, if there is no evidence of any case needing any early intervention, then there is no point in running titers to determine when to begin early intervention.
 

A few references you might find of interest:
Management of Blood Donors and Blood Donations From Individuals Found to Have a Positive Direct Antiglobulin Test. Transfusion Medicine Reviews 2012. Volume 26, Issue 2,  Pages 142-152,
Garratty G. The significance of IgG on red cell surface. Transfus Med Rev. 1987;1:47–57.
Petz LD, Garratty G. Immune Haemolytic Anaemias. 2nd ed. Philadelphia, PA: Churchill Livingstone; 2004.

This is from our ABID SOP (sorry the format is weird): 
a.    Warm Autoantibody Guidelines –(Expert judgment is required on a case-by-case basis to supplement these guidelines.  Contact supervisor or Reference Lab for advice) [return to top]
                        i.        Clues it’s a Warm Auto
1.    Reacts with most or all cells tested—usually at a fairly consistent strength.
2.    Positive DAT.
3.    If it is severe enough that there is hemolytic anemia, the patient would be anemic with a high LDH or bilirubin and high reticulocyte count.  The patient’s plasma sample may appear hemolyzed or icteric.  Haptoglobin would be low.
4.    Contact Blood Bank Supervisor for further consult if uncertain. 
5.    Patient has not taken anti-CD38 (daratumumab/Darzalex/DARA) or anti-CD47 drugs in prior 6 months.
                      ii.        Clues it’s NOT a Warm Auto
1.    Reactivity with most or all cells in gel, usually 2+ or less, varying strength could be HTLA-like antibody or antibody to gel diluent. It’s not uncommon for patients to have a positive DAT without having a detectable warm auto antibody so the positive DAT could be present coincidentally.
a.    To confirm antibody to gel diluent, convert 3% screen cells to 0.8% to run in gel. If negative, turn out the 3-cell gel screen and document situation in the patient record.
b.    An HLTA-like antibody will usually remain detectable (although sometimes weaker) in PEG and even saline techniques.
2.    Alloantibodies:
a.    If patient transfused in the prior 3 months, confer with the most expert person available before calling it a warm-auto.
b.    Elution may produce both a panagglutinin and another specificity or may show only a new alloantibody. The panagglutinin may be so strong a weak allo is undetectable.
c.    If the DAT looks mixed field (repeat IgG DAT in gel for clear-cut mixed field), it may be an allo.
3.    Drug-induced antibody:
a.    Research patient’s diagnoses for multiple myeloma, amyloidosis, or other autoimmune diseases. Look for recent surgeries or infections as a clue for cephalosporin treatment. Research their drug history for cephalosporins and anti-CD38 or anti-CD47 drugs.  There is variability whether these present with only a positive DAT (more common with cephalosporins) or with a negative DAT and positive screen or with both positive.
b.    Rarely, other drugs cause what looks like a warm autoantibody.
                     iii.        When the Auto control (AC) or DAT is positive, first check transfusion history.  The AC could be positive due to a delayed serologic/hemolytic transfusion reaction and NOT a warm auto.  See Positive autocontrol.
                     iv.        If not already done, perform a DAT (Direct Antiglobulin Test Procedure).  Warm autoantibody patients can have RBCs coated with IgG only or IgG and complement both.  Occasionally, only complement may be present.
                      v.        If not already done, perform an antibody panel in gel (or other primary testing method).
                     vi.        People who make warm autoantibodies are more likely to make allo-antibodies as well. We need to identify any allo-antibodies in the sample so we want to avoid detecting the autoantibody if possible but still be able to detect allo-antibodies (at least strong ones).
                    vii.        If reactivity in gel is < 1+ or there are some negative reactions, start a 3% tube PEG antibody screen.  If reactivity in gel is ≥ 1+, start a 3% Saline (no enhancement) 30-minute tube antibody screen.  If amount of specimen is minimal, skip PEG screen and only do saline or, if some negatives, rule out with negative reactions found in gel and run selected cells needed to complete ruling out the usual antibody specificities.
                   viii.        If patient has not been recently transfused and usual specificities can’t be ruled out in tube testing, a PEG Autoadsorption should be considered.  PEG adsorptions should not be attempted with patients who have a strong complement coating.
                     ix.        If can’t rule out usual specificities in tube testing and the patient has been transfused in the past 3 months, send the specimen to the Reference Lab for allo-adsorptions to determine the presence/absence of underlying alloantibodies. See Red Cross (ARC) BloodHub/Connect--Standard Work.  If the patient is too critical to wait for the workup, contact the on-call Pathologist and Blood Bank supervisor.  Phenotypically matched units may be indicated. See Increased Risk Transfusion Release Form. 
                      x.        Turn out ABID results as Warm Autoantibody plus any other specificities detected.
                     xi.        Approach to crossmatching in the presence of warm auto-antibodies:
Situation
Pt Hemolyzing*
XM Methods
XM Results
Enough negs in gel to rule out all usual Ab specificities
Yes
Gel
Incompatible
Enough negs in gel to rule out all usual Ab specificities
No
Gel
Compatible
Can rule out all usual Ab specificities in PEG
Yes
Gel
Incompatible
Can rule out all usual Ab specificities in PEG
No
PEG
Compatible
Can rule out all usual Ab specificities in Saline
Yes
Gel
Incompatible
Can rule out all usual Ab specificities in Saline
No
Saline
Compatible
Alloantibodies identified or can’t rule out some Ab specificities in Saline
Yes
Saline** to assess compatibility with allos, then gel to turn out results
Incompatible
Alloantibodies identified or can’t rule out some Ab specificities in Saline
No
Saline
Compatible
Autoadsorption required and able to rule out usual Ab specificities
Yes or No
Gel with neat plasma
Incompatible
Autoadsorption required and alloantibodies identified or can’t rule out usual Ab specificities
Yes or No
With adsorbed sample** to assess compatibility with allos, then gel with neat sample to turn out results
Incompatible
 
*If patient is hemolyzing, no transfused unit will be truly compatible. Use “incompatible” XM result code in STTx, not “least incompatible” for these cases.
**If second XM method (that’s not to be turned out) is required, record on log sheet.
1.    Warm Auto Notes:
a.    The purpose of the PEG or Saline Antibody screen or PEG adsorption is not to be able to call the primary antibody screen negative, but to rule out underlying alloantibodies.  Generally, these tube ABSC’s will NOT be reported in STTx.
b.    Incubation in the presence of enhancement (gel/PEG) reagents may cause reactivity in the AC that is only an in vitro phenomenon. If the DAT is negative and the AC is positive, antibodies to enhancement constituent or autoantibodies reactive only in enhancement medium should be considered.  An Antibody Elution (Eluate) may help determine the presence/absence of warm autoantibody reactivity.
c.    If the patient is demonstrating active hemolysis, use gel or PEG to crossmatch units. The units still may suffer shortened red cell survival in vivo so calling them incompatible is justifiable.
d.    Consult with Blood Bank Supervisor about performing a full phenotype with the available monoclonal (non-AHG) antisera.  Consider giving phenotypically similar RBCs for transfusion.  If alloantibodies are ruled out in a current specimen, units that are only historically antigen-negative are acceptable.   If we must transfuse before alloantibodies can be ruled out, confirmed antigen-matched units are advised if time permits.
e.    Warm autoantibodies can be confirmed in one of two ways: demonstrate that EGA-treated (antibody removed) pre-transfusion autologous cells react with neat plasma or prove that the antibody reactivity is adsorbed out with pre-transfusion, autologous cells.
f.     Patients on daratumumab (Darzalex or DARA or other anti-cd38 drugs) may appear to have a warm auto antibody but it is actually the drug reacting with the cd38 antigens on the red cells. They may have either a negative or positive DAT and AC.  The only effective way to test these patients is to test against DTT treated cells, recognizing that this will miss antibodies to antigens destroyed by DTT like the Kell system.  These patients benefit from having a pre-treatment antibody screen run and possibly antigen typing for K (and if K positive, for k).  In most cases molecular genotyping may be indicated. See Dithiothreitol (DTT) Treatment and Anti-CD38 Drugs (daratumumab/Darzalex)--Blood Bank Testing.
g.    Additional anti-CD38 drug therapeutics are in clinical trials in addition to Daratumumab (Janssen Biotech) include MOR202 (MorphoSys), Sarclisa -Isatuximab (Sanofi-Aventis), and TAK-079 (Takeda) for treatment of systemic lupus erythematosus, Amyloidosis, or other autoimmune diseases. Daratumumab and Sarclisa are approved for treating multiple myeloma.
h.    CD47 is a glycoprotein expressed on all cells including RBCs and platelets, which usually signals to prevent phagocytosis.  Anti-CD47 blocks this signal targeting cells for destruction. Samples from patients taking anti-CD47 drugs (Hu5F9-G4 or avelumab) will react with everything like a warm auto and the reverse type may be affected like a cold auto. Anti-CD47 interferes with all RBC and platelet serological tests performed including ABO reverse typing. False positive reactions can be seen in all phases of testing (immediate spin, 37°C, and IAT) and with all forms of IAT testing (i.e., tube, gel, solid phase). Reactions with D negative cells may be stronger than with other Rh phenotypes. False negative phenotyping test results can occur due to RBCs heavily coated by anti-CD47. DATs may be falsely negative due to a “blocking effect” caused by high levels of antibody present, but eluates are strongly positive. Plasma interference and strong panreactive eluates are observed as soon as 1 hour after drug infusion. CD47 antigens cannot be denatured with DDT or other common denaturing agents.  It is highly recommended to perform pretransfusion testing, including blood type, antibody screen and extended phenotype (either serological or predictive genotype) before initiating treatment. Using monoclonal Gamma-clone Anti-IgG in indirect antiglobulin testing (which does not detect IgG4 immune classes like anti-CD47) may avoid most of the interference in AHG testing.  Giving antigen-matched units may be an option if full phenotyping is available.  [return to top]
i.      Additional CD47 drug therapies are also in clinical trials and include the CD47 targeting antibodies CC9002 (Celgene), which, like Hu5F9, is also an IgG4 antibody, and the human monoclonal SRF231 (Surface Oncology). CD47 agonists are also in clinical trials. These include TT1-621 (Trillium)31 and ALX148 (ALX Oncology), which are fusion proteins with the Fc region of IgG1 antibody fused to the CD47-binding domain of SIRPα with the goal of interrupting the CD47-SIRPα survival signal. Unlike CD47-targeting antibodies, TT1-621 appears to bind only minimally to human RBCs and interference in pretransfusion testing has not been observed or reported to date.

I always figured that, if it was benign enough in the donor that they met donor requirements, it was likely to be relatively benign in the recipient. Not perfect, of course.

Main practical issue from a transfusion perspective is a positive IAT XM.
If RBC given via electronic issue you would be unlikely to ever know the unit was DAT positive. 

Refresh the page and hover over the words. 

Agree with Dr. Blumberg. The FDA guidance for CSPs states they can be used when "regular platelets are not available or not practical". This sounds like a more prophylactic use of platelets, which is also not practical. If you didn't have anything but CSPs on the shelf, and there is a request to transfuse, I guess it would be up to you as to how much you want to argue with cardiac surgeons for the sake of your inventory, given that these patients are not actively bleeding. 

I should have added that I recognize that some cardiac surgeons transfuse platelets routinely post-bypass in the hope of reducing bleeding.  I suggest this is a traditional practice without the slightest shred of evidence for benefit.  Purely guesswork and expert opinion, for which there is now evidence of harm.   So whether you give cold or room temp platelets probably doesn't matter as (1) there is likely no benefit to either approach,  and (2) there is likely equivalent harm either way. 
So my short answer is it doesn't matter,  but that platelet transfusion to non-bleeding surgical patients likely doesn't help,  and may increase the risk of thrombosis, inflammation and reduced host defenses against post-operative infection. 

This is from our ABID SOP (sorry the format is weird): 
a.    Warm Autoantibody Guidelines –(Expert judgment is required on a case-by-case basis to supplement these guidelines.  Contact supervisor or Reference Lab for advice) [return to top]
                        i.        Clues it’s a Warm Auto
1.    Reacts with most or all cells tested—usually at a fairly consistent strength.
2.    Positive DAT.
3.    If it is severe enough that there is hemolytic anemia, the patient would be anemic with a high LDH or bilirubin and high reticulocyte count.  The patient’s plasma sample may appear hemolyzed or icteric.  Haptoglobin would be low.
4.    Contact Blood Bank Supervisor for further consult if uncertain. 
5.    Patient has not taken anti-CD38 (daratumumab/Darzalex/DARA) or anti-CD47 drugs in prior 6 months.
                      ii.        Clues it’s NOT a Warm Auto
1.    Reactivity with most or all cells in gel, usually 2+ or less, varying strength could be HTLA-like antibody or antibody to gel diluent. It’s not uncommon for patients to have a positive DAT without having a detectable warm auto antibody so the positive DAT could be present coincidentally.
a.    To confirm antibody to gel diluent, convert 3% screen cells to 0.8% to run in gel. If negative, turn out the 3-cell gel screen and document situation in the patient record.
b.    An HLTA-like antibody will usually remain detectable (although sometimes weaker) in PEG and even saline techniques.
2.    Alloantibodies:
a.    If patient transfused in the prior 3 months, confer with the most expert person available before calling it a warm-auto.
b.    Elution may produce both a panagglutinin and another specificity or may show only a new alloantibody. The panagglutinin may be so strong a weak allo is undetectable.
c.    If the DAT looks mixed field (repeat IgG DAT in gel for clear-cut mixed field), it may be an allo.
3.    Drug-induced antibody:
a.    Research patient’s diagnoses for multiple myeloma, amyloidosis, or other autoimmune diseases. Look for recent surgeries or infections as a clue for cephalosporin treatment. Research their drug history for cephalosporins and anti-CD38 or anti-CD47 drugs.  There is variability whether these present with only a positive DAT (more common with cephalosporins) or with a negative DAT and positive screen or with both positive.
b.    Rarely, other drugs cause what looks like a warm autoantibody.
                     iii.        When the Auto control (AC) or DAT is positive, first check transfusion history.  The AC could be positive due to a delayed serologic/hemolytic transfusion reaction and NOT a warm auto.  See Positive autocontrol.
                     iv.        If not already done, perform a DAT (Direct Antiglobulin Test Procedure).  Warm autoantibody patients can have RBCs coated with IgG only or IgG and complement both.  Occasionally, only complement may be present.
                      v.        If not already done, perform an antibody panel in gel (or other primary testing method).
                     vi.        People who make warm autoantibodies are more likely to make allo-antibodies as well. We need to identify any allo-antibodies in the sample so we want to avoid detecting the autoantibody if possible but still be able to detect allo-antibodies (at least strong ones).
                    vii.        If reactivity in gel is < 1+ or there are some negative reactions, start a 3% tube PEG antibody screen.  If reactivity in gel is ≥ 1+, start a 3% Saline (no enhancement) 30-minute tube antibody screen.  If amount of specimen is minimal, skip PEG screen and only do saline or, if some negatives, rule out with negative reactions found in gel and run selected cells needed to complete ruling out the usual antibody specificities.
                   viii.        If patient has not been recently transfused and usual specificities can’t be ruled out in tube testing, a PEG Autoadsorption should be considered.  PEG adsorptions should not be attempted with patients who have a strong complement coating.
                     ix.        If can’t rule out usual specificities in tube testing and the patient has been transfused in the past 3 months, send the specimen to the Reference Lab for allo-adsorptions to determine the presence/absence of underlying alloantibodies. See Red Cross (ARC) BloodHub/Connect--Standard Work.  If the patient is too critical to wait for the workup, contact the on-call Pathologist and Blood Bank supervisor.  Phenotypically matched units may be indicated. See Increased Risk Transfusion Release Form. 
                      x.        Turn out ABID results as Warm Autoantibody plus any other specificities detected.
                     xi.        Approach to crossmatching in the presence of warm auto-antibodies:
Situation
Pt Hemolyzing*
XM Methods
XM Results
Enough negs in gel to rule out all usual Ab specificities
Yes
Gel
Incompatible
Enough negs in gel to rule out all usual Ab specificities
No
Gel
Compatible
Can rule out all usual Ab specificities in PEG
Yes
Gel
Incompatible
Can rule out all usual Ab specificities in PEG
No
PEG
Compatible
Can rule out all usual Ab specificities in Saline
Yes
Gel
Incompatible
Can rule out all usual Ab specificities in Saline
No
Saline
Compatible
Alloantibodies identified or can’t rule out some Ab specificities in Saline
Yes
Saline** to assess compatibility with allos, then gel to turn out results
Incompatible
Alloantibodies identified or can’t rule out some Ab specificities in Saline
No
Saline
Compatible
Autoadsorption required and able to rule out usual Ab specificities
Yes or No
Gel with neat plasma
Incompatible
Autoadsorption required and alloantibodies identified or can’t rule out usual Ab specificities
Yes or No
With adsorbed sample** to assess compatibility with allos, then gel with neat sample to turn out results
Incompatible
 
*If patient is hemolyzing, no transfused unit will be truly compatible. Use “incompatible” XM result code in STTx, not “least incompatible” for these cases.
**If second XM method (that’s not to be turned out) is required, record on log sheet.
1.    Warm Auto Notes:
a.    The purpose of the PEG or Saline Antibody screen or PEG adsorption is not to be able to call the primary antibody screen negative, but to rule out underlying alloantibodies.  Generally, these tube ABSC’s will NOT be reported in STTx.
b.    Incubation in the presence of enhancement (gel/PEG) reagents may cause reactivity in the AC that is only an in vitro phenomenon. If the DAT is negative and the AC is positive, antibodies to enhancement constituent or autoantibodies reactive only in enhancement medium should be considered.  An Antibody Elution (Eluate) may help determine the presence/absence of warm autoantibody reactivity.
c.    If the patient is demonstrating active hemolysis, use gel or PEG to crossmatch units. The units still may suffer shortened red cell survival in vivo so calling them incompatible is justifiable.
d.    Consult with Blood Bank Supervisor about performing a full phenotype with the available monoclonal (non-AHG) antisera.  Consider giving phenotypically similar RBCs for transfusion.  If alloantibodies are ruled out in a current specimen, units that are only historically antigen-negative are acceptable.   If we must transfuse before alloantibodies can be ruled out, confirmed antigen-matched units are advised if time permits.
e.    Warm autoantibodies can be confirmed in one of two ways: demonstrate that EGA-treated (antibody removed) pre-transfusion autologous cells react with neat plasma or prove that the antibody reactivity is adsorbed out with pre-transfusion, autologous cells.
f.     Patients on daratumumab (Darzalex or DARA or other anti-cd38 drugs) may appear to have a warm auto antibody but it is actually the drug reacting with the cd38 antigens on the red cells. They may have either a negative or positive DAT and AC.  The only effective way to test these patients is to test against DTT treated cells, recognizing that this will miss antibodies to antigens destroyed by DTT like the Kell system.  These patients benefit from having a pre-treatment antibody screen run and possibly antigen typing for K (and if K positive, for k).  In most cases molecular genotyping may be indicated. See Dithiothreitol (DTT) Treatment and Anti-CD38 Drugs (daratumumab/Darzalex)--Blood Bank Testing.
g.    Additional anti-CD38 drug therapeutics are in clinical trials in addition to Daratumumab (Janssen Biotech) include MOR202 (MorphoSys), Sarclisa -Isatuximab (Sanofi-Aventis), and TAK-079 (Takeda) for treatment of systemic lupus erythematosus, Amyloidosis, or other autoimmune diseases. Daratumumab and Sarclisa are approved for treating multiple myeloma.
h.    CD47 is a glycoprotein expressed on all cells including RBCs and platelets, which usually signals to prevent phagocytosis.  Anti-CD47 blocks this signal targeting cells for destruction. Samples from patients taking anti-CD47 drugs (Hu5F9-G4 or avelumab) will react with everything like a warm auto and the reverse type may be affected like a cold auto. Anti-CD47 interferes with all RBC and platelet serological tests performed including ABO reverse typing. False positive reactions can be seen in all phases of testing (immediate spin, 37°C, and IAT) and with all forms of IAT testing (i.e., tube, gel, solid phase). Reactions with D negative cells may be stronger than with other Rh phenotypes. False negative phenotyping test results can occur due to RBCs heavily coated by anti-CD47. DATs may be falsely negative due to a “blocking effect” caused by high levels of antibody present, but eluates are strongly positive. Plasma interference and strong panreactive eluates are observed as soon as 1 hour after drug infusion. CD47 antigens cannot be denatured with DDT or other common denaturing agents.  It is highly recommended to perform pretransfusion testing, including blood type, antibody screen and extended phenotype (either serological or predictive genotype) before initiating treatment. Using monoclonal Gamma-clone Anti-IgG in indirect antiglobulin testing (which does not detect IgG4 immune classes like anti-CD47) may avoid most of the interference in AHG testing.  Giving antigen-matched units may be an option if full phenotyping is available.  [return to top]
i.      Additional CD47 drug therapies are also in clinical trials and include the CD47 targeting antibodies CC9002 (Celgene), which, like Hu5F9, is also an IgG4 antibody, and the human monoclonal SRF231 (Surface Oncology). CD47 agonists are also in clinical trials. These include TT1-621 (Trillium)31 and ALX148 (ALX Oncology), which are fusion proteins with the Fc region of IgG1 antibody fused to the CD47-binding domain of SIRPα with the goal of interrupting the CD47-SIRPα survival signal. Unlike CD47-targeting antibodies, TT1-621 appears to bind only minimally to human RBCs and interference in pretransfusion testing has not been observed or reported to date.

Bring back minor crossmatches?

Hi Mabel,

I contacted Jill and, although there was some talk about it, nothing has come of it yet.  The authors are aware, however, that the public would like a new version.

Oh, John, you are missing all the fun!  Everyone wants to give blood pre-hospital now--on air and even ground ambulances.  They prefer WB because it is easier to transfuse, has some platelet activity (yes, cold platelets work for trauma) for the first couple of weeks. and doesn't dilute the coag factors.  It started with the military and then got going in Texas.  With the O blood shortage, we can't give it to ground ambulances who would seldom use it, but we might be talked into providing liquid plasma (group A, never frozen, good for 26 days).  The link below may be educational for you.  Not everyone agrees with the research, but it is increasing everywhere.
STRAC Blood

I'm all for the concept of quality and the strive to provide the safest blood products to patients, but I won't deny that sometimes many of our current practices in blood banking in terms of achieving that "quality" seems excessive, unnecessary, and sometimes it feels like a mere quality charade for inspectors and regulators. Considering the hight cost that blood banks have to incur to meet all quality regulations, it may be worth studying the financial impact of the many quality measures that regulate the practice of blood banking and to what extent these measures are actually contributing to achieving the quality needed to provide the best blood products to patients.

I don't know, although I have heard rumours.

I'll contact Martin Olsson via Jill Storry, but you'll have to give me a couple of days.