Difficult Hysterectomy, large bleeding, NO type and screen-How do we use what we know about DO2

Several years ago I was involved in a case (supervising a CRNA) where the gynecologist had trouble with a hysterectomy and started to lose a little blood.  The blood loss was slow and steady. Therefore, no panic ensued when it was discovered that this patient had inadvertently gone  back to surgery without an up-to-date type and screen.   Furthermore, when we looked in the system, it was discovered that she had had antibodies on her most recent type and screen.  So going forward, a decision had to be made regarding a transfusion trigger given that we would be giving blood that may be incompatible with her antibodies.  I have written peripherally about this issue in a couple of earlier posts in this blog: Acute hemorrhage in obstetrics and antibodies in patient for fem pop from HIT.

In this case we decided to hold off on transfusion as long as there were no overt signs of the patient reaching the inflection point on the VO2 DO2 graph and the Hgb remained above 6 g/dL.

Essentially this meant that we recognized that for this otherwise healthy female, oxygen delivery (DO2) was far in excess of tissue oxygen utilization (VO2).   In fact, for a typical healthy female under anesthesia VO2 will be about 200 mL of oxygen every minute. DO2 is far in excess of this at 780 mL of oxygen per minute. (assuming Hgb of 12 g/dL, C.O. of 5 L/m, sat of 98%). This indicates that we can continue to decrease Hgb without compromising VO2. 

The degree to which anemia can be tolerated while maintaining normovolemia has been carefully reviewed with many published data.  The key parameter in these studies is hemoglobin critical (Hgbcrit), the point where VO2 becomes dependent on DO2, or tissue hypoxia begins.  It has been found to range from as low as 1.1 g/dL up to 4 g/dL in humans.  In general, based on a review, it appears that mortality increases when Hgb gets below 5 g/dL for any sustained amount of time [1]. Unfortunately, this Hgbcrit of 5 g/dL is an average, and it may be much higher in any particular patient (or much lower).  Therefore, patients can sustain a significant drop in Hgb (assuming maintenance of normovolemia) without any significant longterm sequelae. To understand this it is important to understand the physiology underlying oxygen transport and utilization.
If we look at CaO2 (arterial content of oxygen) as Hgb goes from 12 to 4 g/dL we see that at Hgb of 12 we have 1576 mL of oxygen in each dL of blood.  (assume a fixed sat of 98% and PaO2 of 100 mmHg).  As our patient drops to 4 g/dL CaO2 goes to 525 mL.  This is exactly as expected, a 3 fold decrease.  At a cardiac output of 5 L/m, DO2 would now be at 260 mL of oxygen per minute.  This is just above the threshold for total body oxygenation.  But, clearly DO2 does not necessarily drop to this level.  As Hgb drops compensatory mechanisms attempt to maintain DO2 despite a falling CaO2.  First, C.O. increases in order to improve DO2.  The rheologic properties of blood change as it becomes more dilute, allowing for offsetting of afterload aiding in myocardial function.  In awake volunteers,  C.O. is increased predominantly via increased HR.  In anesthetized patients, SV will increase assuming adequate volume loading.  Total body oxygen extraction increases (O2ER).  However, brain and heart tissue maximally extract oxygen at baseline, and therefore rely upon increased perfusion to maintain oxygenation as CaO2 falls. This can occur because the viscosity of blood decreases as it is diluted and also by circulatory redistribution from non critical tissues to critical (i.e. brain/heart).  It is important to remember that DO2 and VO2 as discussed above is total body, and ignores what is going on at the cellular or organ level. This is important since if you were to measure mixed venous saturation and noticed that it remained stable despite a significant drop in Hgb, this does not guarantee that some tissue beds may already have their VO2 dropping due to lack of oxygen, while other tissue beds compensate for this.
In our patient bleeding was occuring yet avoidance of transfusion was important.  While there are large amounts of data and publications on the harmful effects of blood transfusions as well as how to avoid them, clinicians in practice often have a very low threshold to institute transfusion. This is often done using a gestalt of what they think the patient needs based on the basic hemodynamic parameters such as heart rate and blood pressure as they considere the patients medical history.  In our patient, transfusion carried higher risk of harm as there were no units that were antibody matched available. 
 At the time of the case I was unaware of some of the studies looking at this exact scenario. Using a Pig model, Habler O et al. [2] found that after hemodiluting the animals to Hgbcrit (i.e. Hgb level at which signs of tissue hypoxia begin), by using hyperoxic ventilation (HV), they were able to dramatically decrease mortaility (by 85%).  This group took pigs, hemodiluted them to their individual Hgbcrit (indirect calorimetry) while breathing 21% oxygen.  At this point half of the group was switched to 100% oxygen while the rest remained on RA.  Over the next 6 hours this regimen was maintained.  All pigs maintained on RA died.  Only 1 animal died (from 7 total)in the group given 100% oxygen.  After the first 6 hours, the survivors (i.e. those given 100% oxygen) were switched  back to 21% oxygen. Within 3 hours these animals died.  This group took careful measurements of the CaO2 and what portion of it was attributed to oxygen bound to Hgb vs. dissolved in blood. The question becomes, does this article help us understand something different about oxygen utilization that goes against conventional wisdom, i.e. should we not ignore dissolved oxygen as part of the equation of DO2? In this particular study, CaO2 at Hgbcrit on RA went from 4.1 mL/dL to 5.8 mL/dL. This change in content (1.7 mL/dL) was the difference between life and death, and by calculation equals the amount of oxygen that can be carried by 1 g of Hbg (assuming 1 g of Hgb binds 1.39 mL of oxygen and is saturated at 98%).  Feiner et al. have proposed in the Sept 2011 Journal of Anesthesiology, that this additional dissolved oxygen is 100% available to tissues, whereas only a small fraction of Hgb bound oxygen can be extracted.  As proposed by Feiner et al. if you add 94 mmHg to a PaO2, then you will add 0.29 mL/dL of utilizable oxygen (94 x 0.0031).  As it turns out, this is the same amount of utilizable oxygen from 1 g of Hgb (assuming saturation of 97%) [1.34 x (97%-75%)]=0.29 mL/dL.  It should be recognized that this line of reasoning is novel as the traditional teaching of DO2 has focused primarily on the oxygen bound to Hgb while ignoring the dissolved portion.  Feiner et al. published this idea in their recent study highlighted in my previous post where his colleagues were able to show that hyperoxic ventilation reversed the increase in HR accompanying HD to an extent equal to 3 g of Hgb (i.e. transfusion of ~3 units of blood).  Based on the calculations above, 100% oxygen provided an equal amount of usable oxygen (0.29 mL/dL x 3= 0.9 mL/dL).
Other studies have confirmed the benefits of HV ventilation in acute hemodilution (HD) [4].  In Pigs hemodiluted down to a critical Hgb (Hgbcrit) of 2.3 g/dL on RA, switching to 100% enabled a further hemodilution down to 1.2 g/dL [3].  Calculations done in this study are instructive of how the contribution of oxygen from Hgb vs. dissolved changes with a loss of Hgb in dilutional anemia.  According to the authors, a lower threshold for Hgb of 1.5 g/dL exists based on previous studies.  In this situation the oxygen comprising CaO2 comes equally from Hgb bound and dissolved (1.5 g/dL x 1.34 mL/g x 0.98)=1.96 mL/dL Hgb bound; (0.0031 x 650 mmHg)=1.95 mL/dL.  However, the percentage available to tissues is largely from oxygen that is dissolved assuming that only a fraction from Hgb can be extracted and utilized.

So in our particular case, where a blood transfusion was not readily available, it appears from the studies and logic presented that hyperoxic ventilation would be an appropriate temporizing bridge until a matched unit of blood could be made available.   It needs to be underscored that strict maintenance of normovolemia occurred in the above cited studies and would be critical in our patient.  Furthermore, waiting until actual evidence of having reached the Hbgcrit in a clinical situation such as ours (i.e. EKG changes, dramatic decrease in Mixed venous oxygen saturation etc) is not advisable.  These represent inadequate DO2 of the whole body, while other organs may have already reached their threshold.  Therefore, the totality of the patient should be considered (co morbidities, baseline starting Hbg, rate of blood loss, actual achieved PaO2, etc), when deciding the threshold for transfusion. 

In the last part in this series on Hyperoxic ventilation and how it relates to DO2, I will discuss potential negative effects of hyperoxia and consider it's role in DO2 in a patient who is in a low flow state (i.e. severe hypotension during surgery).  Please look for the next entry!!

1. Viele MK, Weiskopf RB. What we can learn about the need for transfusion from patients who refuse blood.  Transfusion 1994;34:396.
2. Meier J, Kemming GI, Wedel-Kisch H, Wolkhammer S, Habler O. "Hyperoxic ventilation reduces 6-hour mortality at the critical Hemoglobin concentration". Anesth 2004;100:76-8.
3. Habler O et al. "Hyperoxic ventilation enables hemodilution beyond the critical myocardial hemoglobin concentration"  Eur J Med Res 2005;10:462-68.
4. Pape A, Meier J, Kertscho H, Steche M, Laout M, Schwerdel F, Wedel M, Zwissler B, Habler O. "Hyperoxic ventilation increases the tolerance of acute normovolemic anemia in anesthetized pigs.  Crit Care Med 2006; 34:1475-82.

A patient with positive Ab screen and acute femoral artery thrombosis

A 62y/o F presents in need of femoral endarterectomy and thrombectomy because of thrombosis precipitated by heparin induced t

ombocytopenia syndrome. The patient had a PMH significant for prior cervical cancer, severe emaciation, chronic anemia, but otherwise had no other relevant medical history.

The had received 4 units of pRBCs 7 days ago to treat a Hgb of 8.1 and it was raised to a peak of 11.1 g/dl, but the hgb had drifted back down to 8.9 g/dl. There was no obvious signs of bleeding. The patient was being treated for thrombosis with an infusion of argatroban at 2 mcg/kg/min and was also receiving IV iron therapy. At the time of surgery her platelet count had rebounded from a nadir of just over 56,000 to above 150,000.

The case was posted as semi urgent by the surgeon. I went to transport the patient from the ICU to the OR and was told that she had no blood available because her T and S (repeated by another physician because her previous type and screen had expired), was positive for antibodies.

This topic has been briefly touched upon in a previous post.

The first portion of this post will deal with the significance of a T&S that comes back positive for antibodies. The second part of this post will briefly review HITS and the pharmacologic options available to the anesthesiologist during surgery.

The type and Screen and the type and Cross: When blood is sent to the blood bank for a type and screen, the blood bank is determining the blood type (A, B, O etc) and also determining the presence of the significant Antigen known as D which is an antigen in on blood cells and is an antigen in the Rh system. If the red blood cells have this antigen they are Rh + (common), but if they do not they are Rh - (about 20 % of the population). This is the type. The screen is looking at the plamsa or serum of the recipient's blood. Now, instead of looking for antigens, the blood bank is screening for antibodies (allo-antibodies) that are unexpected (i.e. non-ABO antibodies). In most patients who have not recieved a transfusion this is negative and a cross match can proceed if needed. In patients who have recently given birth or received a transfusion, it may be positive for unexpected antibodies. This screen is done by incubating the recipients serum or plasma with commercial screening cells that contain all of the critical non-ABO antigens using antihuman globulin (AHG) also known as the indirect antiglobulin test or Coombs test). The antibodies screened for come from seven main antigen systems (MNSs, P, Lewis, Kell, Duffy, Kidd, and sex linked). Go here for a nice table to see the names of the antigens in each antigen system. All of the above described tests take about 45 minutes. In many cases three phases are used for the screen. In phase 1, (the immediate spin) 3 tubes are used and centrifuged looking for agglutination. This phase is often skipped but can be important because it detects reactions due to IgM antibodies which are usually considered nuisance antibodies. Therefore, if this phase is skipped and the phase 3 (coombs phase) is positive, there may be some concern that the positive reaction was a nuisance antibody. Phase 2 is the 37 degree incubation and is required. In phase 3 (coombs phase), is also required, because it detects IgG which are clinically significant antibodies. One further important aspect of the antibody screen is done during phase I, where one test tube is incubated with the patient's own red blood cells which is called the autocontrol. This looks for coating of the red blood cells with antibodies at baseline and indicates possible autoantibodies. However, it can also result from antibodies that have developed from medications that the patients is taking, passively transfused alloantibodies, or alloantibodies coating transfused cells in the patient if they were recently transfused. If this occurs the blood bank should immediately perform a direct antiglobulin test. If this is positive it is a very strong indicator that antibodies are attached to the patient's red blood cells. At this point, if the test is negative and the patient does not have a history of unexpected antibodies in the past, some blood banks will release blood for transfusion after an immediate spin crossmatch or an electronic/computer crossmatch. The immediate spin crossmatch takes about 5 to 10 minutes. The electronic/computer crossmatch may be performed if an FDA approved computer system is available which makes a decision based on a series of validated computer algorithms. The difficult decision going forward in a patient who is in surgery or imminently going to surgery who has a T&S that comes back positive for unexpected antibodies is do you delay potentially necessary surgery to find out what the antibody is and get appropriate blood or do you push ahead? If in surgery the patient is bleeding, at what point does the risk of transfusing a patient w/ unexpected antibodies in a type and screen outweigh the risk of a low Hgb. In animal studies, bleeding animals to very low hemoglobins before transfusing them back up was ok to a point. Once a 3 to 4 hours passed at severely low hemoglobins, irreversible MOD set in and the animal was no longer able to be resuscitated. Essentially this is related to an oxygen debt. Once the oxygen debt becomes too large, no amount of appropriate resuscitation will salvage the organism. The degree of the oxygen debt and thus the chances of survival are a summation of time over which oxygen debt occurs and the degree to which DO2 is below VO2. Once this threshold is reached the triad of acidosis, coagulopathy and hypothermia develops and death follows. Research shows that once this debt is 4,900ml/m^2, mortality is 50%. This results because the vasculaure itself no longer has the energy necessary to vasoconstrict. Therefore, the DO2 critical (the DO2 at which VO2 is dependent on DO2) is the level where an oxygen debt begins to be incurred. In studies this has been found to be between 4 to 7 mL/min/kg (280 to 490 mL/min) for a 70 kg adult. This corresponds to a Hgb of around 5 g/dl assuming a cardiac output of 5.0 l/min. Of course, the metabolic state will also affect this level and a critically ill patient will likely reach DO2 critical before reaching a Hgb of 5.0 g/dl. In practice of course, there is no perfect way to know when your patient has reached DO2 critical and thus needs a transfusion. Nor can we know when we are approaching an oxygen debt of 4,900 mL/m2 (where death is highly likely). Surrogates are needed then. For DO2 critical, the SvO2 is adequate. The other risk to consider is the chance of developing a reaction that is clinically significant when a patient has antibodies. In a large series of studies reviewed by Boisen et al [4], nearly 3,000 patients (11 studies) received nearly 11,000 units of PRBCs of uncrossmatched blood.  The rate of detectable hemolysis was 0.1%.   In the case where a patient is known to have antibodies and blood is transfused that is known to contain the offending (or matching) antigen (Ag), very few patients experiment significant or meaningful hemolysis. In an enlightening study of this very scenario 262 patients with known antibodies were transfused with uncrossmatched blood.  Of these, seven patients were later determined to have received blood that contained antigens that were incompatible with their antibody profile (i.e. the antigens in the transfused blood was able to bind to the antibodies located on the surface of the patients own RBCs).  Of these seven patients, only one had biochemical evidence of hemolysis. This was comprised of elevated LDH and total bilirubin with a decrease in haptoglobin. However, these biochemical changes could be accounted for by other clinical conditions of the patient. Furthermore, the patient did not demonstrate any clinical appearance of issues [3].  In another series of 218 patients who received transfusions with unmatched RBCs, six patients who were found to have detectable and clinically relevant antibodies. None of these six patients suffered hemolysis.  One other patient who did have positive antibodies with a positive coombs test, hemolyzed and later died.  It is unclear whether the hemolysis resulted in the death of the patient however.  In conclusion, transfusing patients with PRBCs that may have antigens that correspond to unexpected antibodies is very unlikely to result in meaningful and acute hemolysis.  Avoiding elective surgery when compatible blood is unavailable is logical; but the clinician should not allow unexpected antibodies delay needed surgery given the unlikely harm that would come should a transfusion be required.

In the end, the decision to proceed to surgery with a patient who has a positive antibody screen means that you consider the benefits of undergoing surgery to outweigh the risk of not having properly matched blood. This risk benefit ratio is not easily arrived at because of the large number of variables.

Part II: Heparin induced thrombocytopenia-This syndrome can be divided into a type I (mild reduction of platelet count with no other sequelae), or type II, a more significant clinical entity with the potential for thrombosis and death. The incidence varies from 1 to 3% of patients receiving heparin and is more common with heparin of bovine origin as opposed to porcine derived heparin. The most significant morbidity from type II HIT is from thrombotic and embolic phenomenon which occurs in 30 to 50% of patients. When this does occur the mortality rate is as high as 30%. The etiology relates to IgG antibodies against the Platelet factor 4-heparin complex which activates platelets via the Fc portion of the antibody. Typically, any patient who has been on heparin and has a significant drop in platelet count on day 4 through 10 of therapy should have a confirmatory ELISA test to detect the presence of serum anti heparin-PF4 Antibodies. Of course, while waiting test results all heparin products should be discontinued. It will take 50 to 100 days before the IgG antibodies against Heparin-PF4 complexes are cleared from the circulation. Therefore, in patients with HIT alternative medications to prevent blood clots are required. In general, those patients who require anticoagulation but have anti-heparin-PF4 antibodies will require inhibition of thrombin directly. The thrombin enzyme has three sites where inhibition can occur, one is a catalytic site (active site) and the other two are known as exosites (1 & 2). Please see figure 1 and 2.

In general the direct thrombin inhibitors (DTI) differ from heparin in the following ways. They are smaller and do not require Antithrombin to function (thus their name direct thrombin inhibitors). They, being smaller, can bind to thrombin that is already fibrin bound, and thus, can help work at the clot site itself as opposed to heparin, which only acts on thrombin which has yet to partake in clot formation. Lastly, there is no agent that can be given to reverse the effects of these medications. Therefore, care must be taken.

Argatroban is a DTI that is univalent and reversible. It is one of two DTIs that are FDA approved for the treatment of HIT in the US. Argatroban has a few advantages over the other FDA approved agent for the treatment of HIT in the US (lepidrudin). First, Lepirudin in case control studies improved outcome for patients with HIT, but with a higher risk of hemorrhage (14% for lepirudin vs 8% for control). This increased risk for bleeding may be related to its slower offset and the fact that it inhibition of thrombin is irreversible. Second, Lepirudin has been associated with fatal anaphylaxis in patients re exposed to lepirudin within 3 months of a previous exposure. Up to 70% of patients treated with lepirudin develop antihirudin antibodies. These antibodies can have paradoxical effects in that in some patients the dose must be reduced because these patients will clear lepirudin more quickly. It is renally cleared so, in my patient, it would not have been a good choice.

Argatroban is metabolized by the liver (and therefore is preferred in patients with renal dysfunction as was my patient). The 1/2 life is 40 to 50 minutes with anticoagulation effects ceasing after 120 minutes. Activity is measure with the aPTT. The medication is started as an infusion at 2 mdg/kg/min and then titrated up to acheive an aPTT of 1.5 to 3 x normal. After starting an infusion the first aPTT can be drawn at about the 2 hour point. It may also be monitored by an ACT. For starting anticoagulation in a patient undergoing PCI who has HIT, an initial starting dose of 25mcg/kg/min and a bolus dose of 350 mcg/kg over 3 to 5 minutes is given. Check ACT after 5 to 10 min to verify if greater than 300 seconds. If less than 300 sec then give another dose of 150 mcg/kg. If an infusion is running, then increase to 30 mcg/kg/min, if the ACT is greater than 450 sec then decrease infusion to 15 mcg/kg/min. In the OR for ACTs that do not need to be greater than 300 sec a case report using Argatroban for CEA states that a loading dose of 150 mcg/kg was used and then followed by an infusion of 5 mcg/kg/min. The goal for the ACT was 200 s in this report [2].

Hirudin is derived from the saliva of the leech (Hirudio medicinalis). It is cleared by the kidneys and therefore is not the first choice in patients with kidney dysfunction. It is immunogenic, with a 44% incidence of antihirudin antibodies. The incidence of anaphylaxis on reexposure is 0.16%, not insignificant.

Bivalirudin (Angiomox) is a small synthetic hirudin molecule. It's clinical use has been relegated for the most part to PCI. However, in the OR it would also be helpful in that it is partially cleaved by thrombin and other plasma enzymes (80%) changing its affinity and thereby resulting in a shorter half-life (about 25 minutes). Although this medication is not approved by the FDA for the treatment of HITS, it has been shown to be effective in OPCAB for anticoagulation [1]. The concluded that for OPCAB, Bivalirudin was an alternative to unfractionated heparin proving to be reliable, rapid onset, and rapid offset. They utilized a bolus dose of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/hr. Their goal was an ACT of 300 sec. They monitored the ACT every 30 min and gave a bolus dose of 0.1 mg/kg to 0.5 mg/kg if the ACT was less than 300 sec.

For anesthesiologists, it is most likely that you will encounter argatroban in your clinical practice dealing with non cardiac surgery patients being treated for HIT. Lepirudin, the other FDA approved treatment is somewhat inferior because of safety concerns when compared to argatroban. The other DTIs are more likely to be used in other clinical scenarios such as for PCI.

1) Koster A, Spiess B, Jurmann M, Dyke C, Smedira N, Aronson S, Lincoff MA. Bivalirudin Provides Rapid, Effective, and Reliable Anticoagulation During Off-Pump Coronary Revascularization: Results of the “EVOLUTION OFF” Trial. A&A, 103(3). 2006.

2) Hallman S., Hebbar L., Robison J., and Uber W. The use of Argatroban for Carotid Endarterectomy in Heparin-Induced Thrombocytopenia. A&A. 100(4); 2005.

3) Goodell PP, Uhl L, Mohammaed M, Powers AA. Am J Clin Pathol 2010; 134:202-6.

4) Boisen ML, Collins RA, Yazer MH, Waters JH. Anesthesiology 2015; 122:191-5

Obstetrical Hemorrhage-A near Miss

On a previously quiet Monday afternoon I received a call from the OB floor. "we are going for a stat c/s" was the report given by the nurse. I headed immediately towards the OB OR. I encountered the patient at the elevators leading to the 6th floor. I breifly got a history from the nurses accompanying the patient. She was 36 years old at 36 weeks gestation. She was experiencing brisk vaginal bleeding associated with severe abdominal cramps and pain. The ambulance decided to divert to our hospital because of the urgency of the situation. She was wheeled straight to the OR and hooked up to monitors. I found out that she had a history of hypertension taking Labetalol, w/ NKDA. She was also known to have a placenta previa w/ possible accreta. She was scheduled by her regular obstetrician to undergo a planned cesarian section and hysterectomy a week or so.

Preinduction VS: BP 120/60 HR 110 RR: rapid sats: 98%. Pt expressing pain and is anxious.

Induction is with ketamine 100mg, fentanyl 50 mcg, sux 90 mg all in rapid sequence with cricoid pressure. After incision, the infant was delivered in 1 minute, and is not in distress.

The patient tolerates induction, has 2 IV lines (20G L and 18G R). Within 5 minutes of induction the plethysmographer tracing goes flat and no blood pressure is able to be recorded. 3 mg of phenylephrine is given IV and the blood pressure returns to 90s/40s. The patient is not typed or crossed so type 0 negative blood is procured on an emergent basis and 2 units of O- PRBCs are given over 20 minutes. A R IJ central line and L rad arterial line are placed with some difficulty. Hemostasis is obtained within 10 minutes of incision. The patient experiences only two more episodes of severe hypotension (30's/10's) and (50's/20's) both treated with epinephrine 0.5 mg bolus. A hysterectomy is performed, ancef 1 gm is given IV, versed is given 2 mg to prevent recall along w/ scopolamine 0.4 mg IV. The patient is intermittent run on 50% nitrous oxide and Desflurane depending on blood pressures. The patient makes 200 mL's of urine for the case, receives 3.5 L crystalloid, 2 u PRBCs (O-), 500 mLs hespan, and EBL is 1500 mL. During the case it is discovered that from faxed medical records she is A- and the specimen states that she has antibodies. The patient remains intubated and is transferred to the ICU. Because she is starting to develop hypotension again, the decision is made to transfuse her units of blood, this time A- matched blood. A Hg drawn after her first two units is 7.9 g/dl. The patient did continue to have brisk bleeding from the vagina immediately after surgery, but this was controlled and no oozing occurred from her central line site or arteral line site. After surgery her PTT came back at >200s (significantly prolonged), however, her fibrinogen level was only mildly low with a normal PT and INR. Upon arrival to the ICU she was 34 C.

This represents a case of severe maternal hemorrhage associated with placental abruption and placenta increta (discovered at operation). Placental abruption is not uncommon occurring in 1/100 to 1/150 deliveries, but is not commonly as severe as in this particular patient. It carries of perinatal mortality of 20%, so rapid delivery is often mandated for fetal and maternal salvage. This patient did have a few risk factors for abruption including advanced maternal age (36 y/o) and history of hypertension. Other risk factors, African american race, multiparity, cigarette smoking and cocaine abuse were either negative or unknown. Patients who experience abruption of the placenta are at high risk for DIC as demonstrated by Gilabert and colleagues in 1985. They explained that large venous sinuses beneath the abrupted placenta could allow thrombopastic material to enter the maternal circulation. Fortunately, in this patient no signs or evidence of DIC presented itself.

Treating hemorrhagic shock typically involves ensuring the maintenance of DO2. Since DO2=CO X (Hb x 1.34 x SaO2) + (PaO2 x 0.0031), maintaining an adequate cardiac output and Hb level are the principal factors. Secondarily, O2 extraction at the tissue level can compensate for decreased DO2. PaO2 in this regard is insignificant and the saturation is usually not so low as to be rendered clinically important in this regard. Initially, colloids and crystalloids should be utilized to maintain cardiac output, which in healthy individuals will easily compensate for a lowered Hb and in some cases DO2 may be elevated after hemorrhage compensated by crystalloid infusion due to improved rheologic effects.

In our case it was decided to transfuse unmatched type O negative blood. According to the ASA committee on transfusion medicine (4th edition), it is recommended to give uncrossmatched type 0 negative blood only when the patient is experiencing signs of organ dysfunction related to decreased O2 delivery. In males and post menopausal females, it is recommneded that type O positive be used. Only 20% of the population is considered Rh -, and therefore, type O Rh-negative blood is less common and should be utilized only when necessary. The concern is that giving a female who is still may yet have children in the future, you may cause her to develop anti-D antibodies (or antibodies against the D antigen in the Rh system). This is referred to as sensitization. In other words, giving type O-positive blood is unlikely to cause any reaction at all to any one unless they are Rh-negative and already sensitized (unlikely unless they have had previous transfusions or pregnancies). In historical studies, patients will develop anti-D antibodies about 80% of the time if they are Rh-D negative and are exposed to Rh positive blood. However, recent studies in trauma victims who require massive ressuscitation with fluid and blood products have found that sensitization occurs in only 30% of these individuals. It is hypothesized that the intense stress response brought on by the trauma or illness suppresses the normal immune response and reduces the likelihood of sensitization. In our case, our patient was required to have a cesarian section followed by hysterectomy and furthermore had received Rhogam. Therefore, O Rh positive blood would probably have been a better choice in retrospect so as to conserve the more rare type O Rh-negative blood. Some may question this approach given that our patient had received Rhogam which acts by destroying fetal RBCs that cross into the maternal circulation. In this case, one might suppose that the Rh immunoglobulin still circulating in the mother, might destroy RBCs transfused if they were type O positive. The standard dose is 300 mcg, and this only destroys about 15 mL of RBCs.
One other caveat in our patient is that she was positive for antibodies, although nothing more was specified. Our pt was type A Rh-negative. This indicates that she most likely received Rhogam (Antibodies) to prevent sensitization of the mother to fetal Rh-positive antigens, thus causing risk in future pregnancies for hemolytic disease of the newborn, a disease in which the fetus' RBCs are attacked as foreign by antibodies that manage to cross the placenta from the mother. Receiving Anit-D antibodies (Rhogam) will cause a subsequent type and screen to show antibodies, but they are unlikely to cause problems. Regardless of whether she had actual antibodies on the type and screen or not, given the patient's dire clinical situation, an emergency transfusion was indicated.
In our patient a sample was immediately sent to the blood bank to do a type and screen. However, in the mean time, 2 units of type O negative blood was given. The type and screen took 15 minutes and a electronic match was performed so that we had type A negative blood in only 30 minutes. A question was raised as to whether the patient could receive her type specific blood now after having received two units of type O negative blood. According to Yao and Artusio textbook, referring to published ASA guidelines, it is recommended to continue using type O negative blood if whole blood is given after only two units. However, whole blood is rarely used today, and the amount of serum in packed cells is very small and quickly diluted into the volume of blood in the patient. Therefore, the recommendation is to switch back to type specific blood even after several units of type O negative packed RBCs. At our institution, the blood bank does not specify a cut off for the number of type O negative blood given before we are unable to switch back to type specific blood.
When a type and screen is done, the screen portion refers to the mixing of the patient's serum with a commercially available donor RBC reagents. RBC surfaces contain up to 300 different antigens. In patients who have not been exposed to blood (transfusion or pregnancy), it is very unlikely that there will be unanticipated antibodies. In these cases, autoantibodies are the most likely culprit of a postive antibody screen. However, it is important to send the blood in a purple top tube (which contains EDTA to prevent a false positive). Certain medications may also result in a false positive: Ibuprofen, penicillins, cephalosporins, tetracyclines, antihistamines, sulfonamides, levodopa, methyldopa are a few of the most notorious ones. Furthermore, an autocontrol may be run and result in a positive. This test reacts the patients serum against their own RBCs and if positive should be followed by a direct antiglobulin test. The Type and Screen takes about 10 minutes. Not all antibodies are clinically relevant, however, when the screen comes back positive for antibodies, i.e., the patient's serum contains antibodies that might cause a hemolytic reaction to a transfusion, the antibody type is not known until further investigation. Clinically significant antibodies are: Anti-A,B, D, C, E, c, e, Fya, Fyb, Kell, Jka, Jkb, S, and s.
In summary, in an emergency use type O Rh positive blood unless you are transfusing a female is might become pregnant in the future; in this case use the more rare blood type O Rh-negative. In an emergency, always send a type and screen even if you are planning on using type O blood and switch to type specific blood as soon as possible. If the screen comes back positive for antibodies, a brief discussion with the lab is in order to find out if this occured at room temperature or at 37C (temp the screen should be done at). In some cases a false positive will occurr (due to medications or treatment received as in our patient Rhogam). Armed with this information, a benefit to risk analysis should ensure quickly to determine whether or not a transfusion is merited in the face of a known positive screen for antibodies.