Hematological complications

HEMATOLOGICAL COMPLICATIONS IN SURGICAL PATIENTS

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medical management of bleeding

Bleeding and cardiac tamponade

Massive hemorrhage

Coagulation disturbances

In the last decade, the understanding of the coagulation process has evolved from a reaction cascade one, with clear-cut separation into the extrinsic and intrinsic pathways, to a dynamic, cell-based model, which values the final phase of the coagulation process and emphatizes the role of the thrombin molecule1,2,3. This conceptual change has led to the need of a more biologically adequate evaluation of the whole hemostasis process, that would comprise the cellular and vascular interactions of the system components, not only the humoral part of the process. This new vision also contemplates the interactions between the hemostasis system and inflammation, cell-signaling and genetic implications, tumour growth, atherosclerosis, spread of metastasis, defense against microorganisms and tissue repair. The endothelium is now seen as an active functional organ that participates intensively in the whole process.

New coagulation model (Membrane- based or Membrane-bound)

INITIATION – production of a small ammount of thrombin

(1)Complex TF + VIIa at the tissue injury site activates X and IX (2) Xa +IXa will lead to the generation of a small ammount of thrombin

AMPLIFICATION – activation of co factors that will amplify coagulation from a small ammount of thrombin generated at the INITIATION phase (1)thrombin activates and recruits platelets (2)thrombin activates cofactores V and VIII (3)thrombin activates factor XI (4)factores and cofactors are produced at the surface of activated platelets: VIIIa, Va and IX a (5)multiple feedback loops amplify the process, triggering the production of a great ammount of complexes

PROPAGATION – formation of a great ammount of complexes that will provoke factor Xá generation at the surface of activated platelets, sustaining the thrombin production, set fibrinogen to fibrin convertion and stabilize the formed clot (1)continued synthesis of complexes in cascade fashion at the activated platelets´surface (2)prothrombin conversion into thrombin (3)tenase complex origins prothrombinase complex (4)conversion of fibrinogen into fibrin and further clot stabilization with the effective crosslinking of the fibrin molecules

LYSIS – break down of clots and formed fibrin strands through the action of plasmin (1)Thrombin binds to thrombomodulin and activates protein C and TAFI (2)Protein C activates fibrinolysis (3) tPA activages fibrinogen (4)Plasminogen is converted into plasmin (5)Fibrin undergoes cleavage and fibrin monomers are liberated into the circulation. (6)Fagocytic mononuclear system is mobilized to remove fibrin monomers and further fibroblasts´ growth stimuli take place

The disappointment with the global coagulation tests, regarding their ability to predict bleeding risk and to guide blood component therapy soon made necessary the development of new strategies for monitoring blood coagulation in the critical care and surgical scenario, giving to the surgical and intensive care team more accurate tools to define the decision-making process during surgical procedures and at the bedside when facing a bleeding or thrombotic complication4,5,6,7,8.

Preoperative coagulation screening4,9,10,11,19

The value of routine coagulation screening with global coagulation tests such as aPTT and prothrombin time with INR have been severely questioned in several trials, and definitely they are not indicated before low-risk procedures if the patient has no history of bleeding tendencies nor clear signs of bleeding diathesis at physical examination. The usefulness of such tests before intermediate and major procedures without previous objective interview with a physician is also questionable. The term‘‘screening” should be properly reserved for patients who do not have Signs and symptoms of underlying abnormality and who are free of any Known conditions that increase the likelihood of abnormal results. Screening tests are useful when they:

1.Cost little 2.Are consistent 3.Carry negligible risk 4.Demonstrate high sensitivity and selectivity 5.Offe high positive and negative predictive value 6.Accurately foreshadow surgical morbidity 7.Are appropriate to the population at hand 8.Uncover common conditions contributing to surgical morbidity and for which effective intervention is available

A careful anamnesis and physical examination is the best screening procedure insofar. Aspects that must be actively searched in the anamnesis are: symptoms of renal and liver disease, family history of bleeding diathesis or fetal losses, bleeding after labour procedures, bleeding gums after brushing the teeth, methrorragia, easy bruising, hematuria, hemoptysis, epistaxis, a history of dark stools without the use of any medication, bleeding after dental procedures, use of medications such as aspirin, clopidogrel, NSAIDS, warfarin, coumadin, dypiridamole, ticlopidine, gingko biloba and others. At physical examination echymoses, petechiae, liver or spleen enlargement, prominent lymphnodes, ascites, spider telangiectasias, skin paleness, limb and eyelid oedema, etc.

PREVALENCE OF HEMATOLOGICAL ABNORMALITIES IN PREOPERATIVE SCREENING19

TEST NUMBER OF PATIENTS PREVALENCE OF ABNORMALITY

HEMOGLOBIN 9363 1.8%

LEUKOCYTES

5359

0.7%

PLATELETS

8670 0.9%

PROTHROMBIN TIME

4786 0.3%

ACTIVATED PARTIAL THROMBOPLASTIN TIME

2955 6.5%

The overall incidence of hemoglobin abnormalities in a combined review of 9363 patients was 1.8% ,but anemia occurs in 4% to 9% of patients 70 years of age and older and predicts the need for transfusion in Patients at risk for blood loss. The prevalence of an elevated white blood cell count in a combined review of 5359 patients was less than1% and was unrelated to perioperative morbidity. The prevalence of platelet abnormalities in a combined review of 8670 patients was calculated to be 0.9%. The abnormality in the preponderance of cases was thrombocytopenia, but management was changed in only 0.02% of cases 19.

Bleeding time and platelet function analysis14,15,16,17,20

Screening with bleeding time is a controversial measure, despite the intense variability of results depending on technique. The Ivy method is the most reliable. There is good evidence suggesting that bleeding time offers no advantage when performed in normal reference populations, however in a cardiovascular patient population where platelet antiaggregation is the rule, this picture might be different. Bleeding time is a good way to detect abnormalities of platelet function, which are increasingly common in the aging population because of regular aspirin and clopidogrel use for primary and secondary prophylaxis in ischemic heart disease and cerebrovascular occlusive disease. Newer methods to evaluate platelet function have been released into the market, and their utility in this regard remains to be determined, despite some promising results. There have been discrepancies in results between some of these devices and other tests such as platelet receptor polymorphism analysis and P-selectin expression, especially in the scenario of aspirin resistant and clopidogrel resistant patients´evaluation but small series of patients demonstrate that these devices may have a role in bleeding risk prediction in the cardiac surgery setting. A prolongued closure time in the PFA 100 analysis in the absence of previous medication use should prompt an investigation on platelet disturbances such as von Willebrand disease, gray platelet syndrome, Bernard Soulier, Glanzmann thrombastenia, storage pool and transduction signaling disturbances. Platelet immunophenotyping and average platelet aggregation studies might be in order in this case. PFA-100 also can be used to guide platelet transfusions and desmopressin administration, it is non invasive, easy to perform and recquires only 0,8 ml of blood for each cartridge. The system reproduces the shear stress effect upon blood cells, which can be an advantage over average platelet aggregometry. However platelet counts below 80 000/mm 3 or a blood hematocrit below 30% will produce prolongation of the closure time, even if there are no platelet abnormalities. PFA 100 is more reliable and produces more reproducible results than the bleeding time20.

Platelet function evaluation devices:

- Platelet function analyzer 100 – PFA – 100 - Dade Behring

- Multiplate platelet function analyzer – Dynabyte medical (www.multiplate.net)

- Ultegra Verify now - Accumetrics

- Helena Plateletworks – Helena

Clot signature analysis with the SonoClot device is also under study for the purpose of bleeding risk prediction, and may have an interesting role in the trauma and cardiac surgery scenario, as well as thromboelastography. Thromboelastography has been used with limited success to predict blood loss in patients undergoing cardiac surgery. A recent prospective study of 255 consecutive patients used a combination of ROTEM and PFA 100 to assess their predictive value. The best prediction came from post cardiopulmonary bypass when a combination of alpha angle and ADP- PFA results gave the best predictive accuracy (Cammerer et all, 2003) If there are any data from the anamnesis and physical examination that suggests the presence of a coagulopathy, a screening protocol must be changed into a diagnostic protocol. The Johns Hopkins risk Classification system allows a classification of surgical risk that factors anticipated blood loss into the risk of surgery. It can be used alone or in combination with other classification systems – associating category I (minimally invasive) with little or no blood loss, category II (minimally to moderately invasive) with blood loss less than 500 ml, category III (moderately to significantly invasive) with blood loss potential of 5000 to 1500 mL and categories IV and V ( both considered highly invasive) with blood loss in excess of 1500 ml. In the presence of an abnormality in screening tests, in the physical examination and anamnesis report, it´s advisable to start a diagnosis protocol even in the small risk categories.

Diagnostic protocols depend on the resources available. If you have thromboelastography available a reasonable one is depicted below, already depicting the measures that might be appropriate after proper diagnosis12,14.19,20.

INTEM – evaluates the intrinsic pathway EXTEM – evaluates the extrinsic pathway FIBTEM – evaluates the participation of platelets and fibrinogen in the coagulation APTEM – assay with aprotinin that shows reversal of lysis time alterations in patients with fibrinolysis when compared to INTEM HEPTEM – assay with heparinase, identifies heparin action.