EVALUATION OF THE PATIENT WITH A POSSIBLE BLEEDING DISORDER
There are three general clinical settings in which patients may be required to undergo evaluation for a possible bleeding disorder. • history or physical signs of bleeding • asymptomatic patients may be incidentally discovered to have laboratory abnormalities • patients may be asked to undergo routine testing history • spontaneous bleeding episodes • response to specific hemostatic challenges • previous surgery or trauma • Circumcision, • Tonsillectomy, • Labor And Delivery, Menses, • Dental Procedures, • Vaccinations, And Injections.
the history of normal blood clotting after such challenges in the recent past is at least as important to note because it may provide a better test of systemic hemostasis than any laboratory measurement could provide.
history of excessive or unexplained bleeding determine whether the cause is a systemic coagulopathy or an anatomic or mechanical problem (This situation is most frequently encountered in postoperative patients with excessive bleeding) ØA history of prior bleeding Øfinding of bleeding from multiple sites Øa single episode of bleeding from an isolated site may be the initial manifestation of a systemic coagulopathy Øinclude a survey of coexisting systemic diseases and durg ingestion that may affect hemostasis. Ørenal failure Ømyeloproliferative disorders Øqualitative platelet abnormalitie Øconnective tissue disease and lymphomas Øliver disease ØAspirin Øantibiotics Øfamily history Ønegative history does not exclude a familial etiology Øfor example, up to 20% of patients with classic hemophilia have a completely negative family history of bleeding
ØPatterns of clinical bleeding Øpatients with thrombocytopenia or qualitative platelet and vascular disorders Øpresent with bleeding from superficial sites in the skin and mucus membranes Øpatients with inherited or acquired coagulation factor deficiencies, such as hemophilia or therapeutic anticoagulation , Øtend to bleed from deeper tissue sites (e. g. , hemarthroses, deep hematomas, retroperitoneal hemorrhage) and in a delayed manner after trauma.
screening tests (1)platelet count, (2) bleeding time (3) prothrombin time (PT), and (4) activated partial thromboplastin time (a. PTT)
Platelet counting Normal range 1500000 - 450000 Bleeding tendency with major trauma <800000 -1000000 Bleeding tendency with minor trauma <500000 Spontaneous bleeding <200000 Sever spontaneous bleeding <100000 "Pseudothrombocytopenia EDTA anticoagulants, or cold agglutinins acting at room temperature it has no known pathologic correlates
LABORATORY TESTS TO ASSESS HEMOSTATIC FUNCTION – Platelet counting and the peripheral smear EDTA-dependent agglutinins are present in approximately 0. 1 percent of people in the general population
bleeding time platelet–vessel wall interactions The bleeding time is prolonged in (1) thrombocytopenia, (2) qualitative platelet abnormalities, (3) defects in platelet–vessel wall interactions (e. g. , von Willebrand's disease), or (4) primary vascular disorders.
A prolonged bleeding time in the absence of thrombocytopenia drugs coexisting diseases ( for example: renal failure )
FORMATION OF THE PLATELET PLUG The functional response of activated platelets involves four different processes: • • Adhesion – the deposition of platelets on the subendothelial matrix Aggregation – platelet-platelet cohesion Secretion – the release of platelet granule proteins Procoagulant activity – the enhancement of thrombin generation.
Platelet activation ADP and epinephrine are relatively weak platelet activators, while collagen and thrombin are the most potent platelet activators. The intact endothelium prevents the adherence of platelets by the production of nitric oxide and prostacyclin. Patients with GPIa-IIa deficiency generally have mild bleeding diathesis, while severe spontaneous bleeding has been reported with platelet GPVI deficiency.
Platelet adhesion primarily mediated by the binding of platelet surface receptor GP Ib-IX-V complex to von Willebrand factor (v. Wf) in the subendothelial matrix Platelet aggregation GP IIb/IIIa receptor on the platelet surface, leading to binding of both immobilized v. Wf and fibrinogen The association of fibrinogen with GP IIb/IIIa is further stabilized by thrombospondin, which is released from platelet alpha granules upon stimulation and binds to fibrinogen and its receptor GPIV (CD 36)
Platelet secretion ADP and serotonin stimulate and recruit additional platelets Fibrinogen is released from platelet alpha granules, providing a source of fibrinogen at sites of endothelial injury in addition to that present in plasma [ Thromboxane A 2, a prostaglandin metabolite, promotes vasoconstriction and further platelet aggregation. Growth factors, such as platelet-derived growth factor (PDGF), have potent mitogenic effect on smooth muscle cells.
following platelet stimulation (eg, by thrombin, collagen or ADP), GP IIb/IIIa undergoes a conformational change and is converted from a low affinity to a high affinity fibrinogen receptor, a process referred to as "inside-out" signaling. "outside-in" integrin signaling the cytosolic portion of the activated GP IIb/IIIa complex binds to platelet cytoskeleton and can mediate platelet spreading and clot retraction, which has been
Prothrombin time Activated partial thromboplastin time
DIAGNOSTIC APPROACH three initial tests should be performed – platelet count, PT, and a. PTT assays are stable for up to eight hours, except for patients receiving unfractionated heparin therapy Heparinized samples, when stored uncentrifuged at room temperature, demonstrate a clinically significant shortening of the a. PTT at four hours Prothrombin time results are stable for up to 24 hours after phlebotomy, remaining constant regardless of storage conditions
OBTAINING THE BLOOD SAMPLE • Whole blood is collected into citrated anticoagulant, in the ratio of one part citrate solution to nine parts blood • If the patient is polycythemic (hematocrit >55 percent), the amount of plasma in the sample is reduced; as a result, the volume of citrated anticoagulant solution needs to be decreased proportionately • The sample must be free of tissue fluids, intravenous solutions delivered through indwelling lines, and heparin. • a two syringe technique • should be mixed gently by inversion three or four times • sent to the laboratory in an expeditious manner, and tested within two hours if kept at room temperature (22 to 24°C) or within four hours if kept cold (2 to 4°C. (
PROTHROMBIN TIME Causes of prothrombin time prolongation • Vitamin K deficiency • Severe liver disease • Deficiency or inhibition of factors VII, X, II (prothrombin), V, or fibrinogen • The infrequent antiphospholipid antibodies (lupus anticoagulant phenomenon) with antiprothrombin activity • While treatment with heparin does not normally prolong the PT (due to the addition of heparin-neutralizing materials to the PT reagent), the PT may be transiently elevated after heparin bolus administration.
PROTHROMBIN TIME Monitoring of warfarin therapy The anticoagulant effect of warfarin is delayed until the normal clotting factors are cleared from the circulation, and the peak effect does not occur until 36 to 72 hours after drug administration During the first few days of warfarin therapy the intrinsic coagulation pathway that does not require factor VII remains intact Equilibrium levels of factors II, IX, and X are not reached until about one week after the initiation of therapy. Measurement of INR International Normalized Ratio or INR ISI INR = [Patient PT ÷ Control PT[ The ISI (international sensitivity index) should be determined for each PT reagent and instrument combination is used to monitor warfarin therapy it may not be directly applicable to patients with liver disease
PROTHROMBIN TIME it is useful to have the ISI value confirmed within each laborator therapeutic range for the INR varies with the clinical indication For most indications (eg, prevention and treatment of venous thromboembolism, atrial fibrillation, and valvular heart disease) the recommended range is 2 to 3. 2. 5 to 3. 5 for patients with a tilting disk valve or bileaflet mechanical valves in the mitral position, patients with a bileaflet mechanical aortic valve who have atrial fibrillation, patients with the antiphospholipid antibody syndrome after a thrombotic event More intense anticoagulation may be indicated when there is extension of clot despite maintenance of a therapeutic INR.
PROTHROMBIN TIME Monitoring warfarin therapy with the INR in patients with the antiphospholipid antibody syndrome alternative methods of monitoring warfarin effect which are insensitive to the presence of a lupus anticoagulant are required • Use of a chromogenic factor X assay • Use of the prothrombin-proconvertin time instead of the INR (not available in the United States( • Use of a commercial reagent insensitive to the patient's particular anticoagulant.
ACTIVATED PARTIAL THROMBOPLASTIN TIME The test is performed by recalcifying citrated plasma in the presence of a thromboplastic material that does not have tissue factor activity (hence the term partial thromboplastin) and a negatively charged substance such as kaolin, which results in contact factor activation, thereby initiating coagulation via the intrinsic clotting pathway Causes of a. PTT prolongation
ACTIVATED PARTIAL THROMBOPLASTIN TIME Monitoring of heparin therapy The critical therapeutic level of heparin to be reached within 24 hours (as measured by the a. PTT) is 1. 5 times the mean of the control value or the upper limit of the normal a. PTT range. The goal of maintenance heparin therapy is to maintain the a. PTT in the range of 1. 5 to 2. 5 times the patient's a. PTT baseline value This level of anticoagulation corresponds roughly to a heparin blood concentration of 0. 2 to 0. 4 units/m. L by the protamine sulfate titration assay, 0. 3 to 0. 6 units/m. L by the anti-factor Xa assay, and 0. 3 to 0. 7 units/m. L by the chromogenic anti-factor Xa heparin assay
ACTIVATED PARTIAL THROMBOPLASTIN TIME Monitoring of heparin therapy low-molecular-weight heparins (LMWHs) inactivate factor Xa, but they have a lesser effect on thrombin because most of the molecules are not long enough to bind to thrombin and AT simultaneously. However, laboratory monitoring is not necessary in nonpregnant patients because the anticoagulant response (anti-Xa activity) to a fixed dose of LMW heparin is highly correlated with the patient's body weight, and there is little correlation between anti-Xa activity and either bleeding or recurrent thrombosis If necessary, monitoring can be performed by testing for anti-factor Xa activity.
With a few notable exceptions, as follows, normal results for all four of the screening tests of hemostasis essentially exclude any clinically significant systemic coagulopathy The PT and a. PTT detect only more severe deficiencies of coagulation factors, generally involving levels of less than 30% of normal; therefore, specific factor levels should be determined if a mild coagulation factor deficiency is suspected.
exceptions ØPatients with von Willebrand's disease sometimes have normal bleeding times and usually do not have sufficiently reduced levels of Factor VIII to affect the a. PTT ØRare disorders of fibrinolysis may also be associated with normal screening tests, necessitating more specialized tests when indicated. ØFactor 13 deficeinc y
THROMBIN TIME measures the final step of the clotting pathway, the conversion of fibrinogen to fibrin. The test is performed by recalcifying citrated plasma in the presence of dilute bovine or human thrombin and recording the time in seconds for a clot to form Causes of thrombin time prolongation • The presence of heparin, a direct thrombin inhibitor such as hirudin, hirulog, or argatroban, or heparan-like compounds (eg, danaparoid, see "New anticoagulants. I", section on Direct thrombin inhibitors. ( • The presence of fibrin or fibrinogen degradation products • Hypofibrinogenemia (<100 mg/d. L), dysfibrinogenemia, or hyperfibrinogenemia (>400 mg/d. L( • Bovine thrombin antibodies from prior exposure to bovine thrombin (only when tested using bovine thrombin reagent; TT will be normal if tested using human thrombin reagent( • High concentrations of serum proteins, as in multiple myeloma and amyloidosis.
Reptilase time found in the venom of Bothrops snakes it differs from thrombin by generating fibrinopeptide A but not fibrinopeptide B from fibrinogen and by resisting inhibition by heparin via antithrombin III All of the causes which prolong the TT, except heparin, also prolong the RT. Thus, the RT is useful for determining if heparin is the cause of a prolonged TT
Thrombin inhibitors direct thrombin inhibitors such as hirudin, hirulog, and argatroban are associated with prolongation of all clotting tests, including the PT, a. PTT, TT the reptilase time in contrast to heparin Argatroban, and probably the other direct thrombin inhibitors, can be effectively monitored with use of the a. PTT or activated clotting times but it interferes with the INR and a. PTT for monitoring concomitant warfarin and heparin therapy, respectively
EVALUATION OF ABNORMAL CLOTTING TIMES • If the a. PTT is prolonged and the PT is normal • If the a. PTT is normal and the PT is prolonged • If both the a. PTT and PT are prolonged • If the TT is normal, the problem resides in the common pathway • Common acquired conditions giving a prolonged PT and a. PTT and a normal TT are • liver disease, • disseminated intravascular coagulation, • and the administration of coumadin • If both the a. PTT and the PT are normal in a patient with an apparent bleeding diathesis
Shortening of clotting times shortening of clotting times (PT, a. PTT, or TT) reflects poor sample collection or preparation techniques clotting factors may be increased or activated in vivo, as in malignancy, disseminated intravascular coagulation, or following short-term exercise, resulting in shortening of clotting times, especially the a. PTT A shortened clotting time that does not appear to reflect technical error is occasionally associated with an • increased risk of thrombosis, • recurrent miscarriage, or • bleeding
Mixing studies There are three important principles underlying such mixing tests • As a general rule, clotting tests will give normal values when 50 percent activity of the involved coagulation factors are present Thus, if the test remains abnormal after 1: 1 dilution, an inhibitor was the cause of the abnormal test. • Some inhibitors may give normal results when tested immediately after 1: 1 dilution; incubation of the diluted sample for up to two hours may resolve this issue. As an example, delayed reactivity is characteristic of factor VIII inhibitors • The presence of heparin in the sample • Antiphospholipid antibodies; these are more commonly associated with a hypercoagulable state rather than bleeding. • Inhibitors of thrombin, such as fibrin or fibrinogen degradation products. These can be detected using a variety of assays (such as fibrin degradation products or Ddimer. ( • Inhibitors to other factors. These are less common and are detected by individual factor assays.
The presence of a factor inhibitor is suspected when the prolonged test, such as the a. PTT, does not correct or only partially corrects following an immediate assay of a 1: 1 mix of patient and normal plasma In some cases, such as acquired factor VIII antibodies, the a. PTT may correct immediately after mixing, but becomes prolonged after 60 to 120 minutes of incubation antiphospholipid antibodies (lupus anticoagulant) also can produce a prolonged a. PTT that is not correctable with normal plasma. The effect of these antibodies on the a. PTT can be overcome by adding excess platelet phospholipid (particularly a hexagonal phase phospholipid) or by assessing the diluted Russell's viper venom time
Tests for specific factor deficiencies and inhibitors An elevated a. PTT can be due to the absence of a factor or the presence of an inhibitor performing a PT or a. PTT on a 1: 1 mix of patient and normal plasma Specific factor deficiencies are then determined by assessing the PT or a. PTT in mixes of test plasma with commercially available plasmas deficient in known factors Factor levels can be functionally assessed by comparing test results to standard curves generated by mixtures of serially diluted normal plasma and factor-deficient plasma. Immunologic and functional assays should give equivalent results when there is factor deficiency. . A low functional assay but normal immunologic assay indicates a functionally abnormal factor.
Evaluation of the Asymptomatic Patient With Abnormal Coagulation Tests contact activation coagulation factors (Factor XII, high-molecular-weight kininogen, prekallikrein) characteristically have a markedly prolonged a. PTT, yet they clearly do not have a clinical bleeding tendency lupus anticoagulants typically have prolongations of the a. PTT, and sometimes also the PT; yet they more often have thrombotic rather than bleeding complications In patients with heparin-induced thrombocytopenia, a marked decrease in the platelet count is sometimes associated with arterial and venous thrombosis. critically important to view the clinical setting, history, physical examination, and screening laboratory tests as complementary facets of the approach to patients with suspected coagulopathies
Evaluation of the Preoperative Patient is not only uninformative but may even be counterproductive when follow-up testing causes unnecessary expense and delays in the surgery. Preoperative bleeding time, PT, and a. PTT do not predict surgical bleeding risk in patients who are not found to be at increased risk on clinical grounds, so a thorough clinical assessment should serve as the guide to the need for obtaining these preoperative screening tests.
Laboratory testing, and possibly further specialized tests of coagulation, is clearly indicated vin patients whose bleeding histories are suspicious for a hemostatic abnormality. vin patients in whom adequate clinical assessment is impossible , vwho are to undergo procedures in which even minimal postoperative hemorrhage could be hazardous.
DIAGNOSTIC APPROACH three initial tests should be performed – platelet count, PT, and a. PTT assays are stable for up to eight hours, except for patients receiving unfractionated heparin therapy Heparinized samples, when stored uncentrifuged at room temperature, demonstrate a clinically significant shortening of the a. PTT at four hours Prothrombin time results are stable for up to 24 hours after phlebotomy, remaining constant regardless of storage conditions
Thrombin time and reptilase time Reptilase, a thrombin-like snake enzyme, differs from thrombin by generating fibrinopeptide A but not fibrinopeptide B from fibrinogen and by resisting inhibition by heparin via antithrombin III Fibrin-strand cross-linking (mediated by factor XIII) is not measured by these assays. Prolonged thrombin times and reptilase times may be due to hypofibrinogenemia, structurally abnormal fibrinogens (dysfibrinogens), or increased fibrin split products Since heparin prolongs the TT but not the RT, the RT is useful for determining if heparin is the cause of a prolonged TT
Tests for specific factor deficiencies and inhibitors An elevated a. PTT can be due to the absence of a factor or the presence of an inhibitor performing a PT or a. PTT on a 1: 1 mix of patient and normal plasma Specific factor deficiencies are then determined by assessing the PT or a. PTT in mixes of test plasma with commercially available plasmas deficient in known factors Factor levels can be functionally assessed by comparing test results to standard curves generated by mixtures of serially diluted normal plasma and factor-deficient plasma. Immunologic and functional assays should give equivalent results when there is factor deficiency. . A low functional assay but normal immunologic assay indicates a functionally abnormal factor.
The presence of a factor inhibitor is suspected when the prolonged test, such as the a. PTT, does not correct or only partially corrects following an immediate assay of a 1: 1 mix of patient and normal plasma In some cases, such as acquired factor VIII antibodies, the a. PTT may correct immediately after mixing, but becomes prolonged after 60 to 120 minutes of incubation antiphospholipid antibodies (lupus anticoagulant) also can produce a prolonged a. PTT that is not correctable with normal plasma. The effect of these antibodies on the a. PTT can be overcome by adding excess platelet phospholipid (particularly a hexagonal phase phospholipid) or by assessing the diluted Russell's viper venom time
CONTROL MECHANISMS AND TERMINATION OF CLOTTING Antithrombin III neutralizes most of the enzymes in the clotting cascade, especially thrombin, factors Xa, and IXa, as well as factor XIIa and factor XIa, The binding of endogenous or exogenous heparins to the heparin binding site on AT III produces a conformational change in AT III which accelerates the inactivating process 1000 to 4000 fold
Tests for fibrinolysis Fibrin-fibrinogen degradation products (FDP) The assays do not differentiate between fibrin degradation products and fibrinogen degradation products of fibrin D-dimers which are degradation products of cross-linked fibrin The method of choice is the enzyme-linked immunosorbent assay (ELISA euglobulin lysis time is less useful for assessing fibrinolysis since results from this test may vary significantly in relation to calcium ion concentrations as well as plasma levels of tissue plasminogen activator and plasminogen activator inhibitor-1
Evaluating antiphospholipid antibodies suggested by the presence of a prolonged a. PTT which does not correct after 1: 1 dilution with normal pooled plasma in a nonbleeding patient with or without a known rheumatologic disorder. addition of phospholipid corrects the clotting time confirms the presence of the lupus anticoagulant phenomenon. Clotting tests can be made more sensitive to the presence of APLA by Øreducing the concentration of lipid material (dilute PT or PTT) Øincreasing preincubation times, or activating coagulation factors in vitro with kaolin (kaolin clotting time) or dilute Russell viper venom. ØIn this setting, the dilute Russell's viper venom time (d. RVVT) is particularly sensitive to the presence of anti-2 -ﻙ glycoprotein I antibodies (which are most closely correlated with thrombotic events), while the kaolin clotting time is more sensitive to antiprothrombin antibodies
von Willebrand disease moderate to severe mucocutaneous bleeding prolonged a. PTT In some patients, however, the clinical manifestations are mild, the a. PTT is normal, and further studies are necessary to make the diagnosis This is particularly true when factors which increase v. Wf and factor VIII levels such as pregnancy, oral contraceptive use, and liver disease are present. Useful tests include bioassay of factor VIII, immunoassay of v. Wf antigen, and measurement of ristocetin cofactor activity Repeated testing is required to establish the diagnosis of v. Wd in some individuals because the results vary over time
Evaluating antiphospholipid antibodies there is currently no standardized test for the lupus anticoagulant phenomenon, and no internationally accepted reference or control materials. The presence of an APLA is confirmed by demonstrating correction of the clotting time by added phospholipid. This can be in the form of hexagonal phospholipid, or phospholipid from freeze-thawed platelets
Evaluating the presence of heparin in the sample in evaluating an isolated prolonged a. PTT or TT This is especially important in hospitalized patients, in whom blood is often drawn from heparinized venous access devices The simplest approach is to redraw a blood sample using an uncontaminated peripheral vein. • Perform a TT and RT. Heparin is present if the TT is prolonged and the RT is normal. • If a prolonged TT is normalized after the addition of protamine or a commercially available ion exchange resin (Heparsorb), heparin or a heparin-like material is present.
Disseminated intravascular coagulation CLINICAL MANIFESTATIONS
Disseminated intravascular coagulation CLINICAL MANIFESTATIONS
Disseminated intravascular coagulation CLINICAL MANIFESTATIONS
Disseminated intravascular coagulation CLINICAL MANIFESTATIONS
Disseminated intravascular coagulation CLINICAL MANIFESTATIONS
Disseminated intravascular coagulation CLINICAL MANIFESTATIONS Acute DIC In one series of 118 patients with DIC, the main clinical manifestations were bleeding (64 percent), renal dysfunction (25 percent), hepatic dysfunction (19 percent), respiratory dysfunction (16 percent), shock (14 percent), thromboemboli (7 percent), and central nervous system involvement (2 percent)
Disseminated intravascular coagulation CLINICAL MANIFESTATIONS Acute DIC Hepatic dysfunction Jaundice is common due both to liver disease hemolysis hepatocellular injury may be produced by sepsis and hypotension Pulmonary disease Pulmonary hemorrhage hemoptysis and dyspnea Diffuse pulmonary microthrombosis DD : sepsis, trauma, and amniotic fluid embolism are causes of acute respiratory distress syndrome (ARDS) as well as DIC
Disseminated intravascular coagulation CLINICAL MANIFESTATIONS Acute DIC Central nervous system dysfunction coma, delirium, and transient focal neurologic symptoms. Microthrombi, hemorrhage, and hypoperfusion
Disseminated intravascular coagulation CLINICAL MANIFESTATIONS Chronic DIC Compensated or chronic DIC develops when blood is continuously or intermittently exposed to small amounts of tissue factor and compensatory mechanisms (liver and bone marrow) are largely able to replenish the depleted coagulation proteins
Disseminated intravascular coagulation CLINICAL MANIFESTATIONS Chronic DIC either asymptomatic with increased levels of fibrin degradation products or has manifestations of venous and/or arterial thrombosis have minor skin and mucosal bleeding. Malignancy, particularly solid tumors, is the most common cause of chronic DIC.
Disseminated intravascular coagulation CLINICAL MANIFESTATIONS Chronic DIC Venous thromboses commonly present as deep venous thrombosis in the extremities or superficial migratory thrombophlebitis (Trousseau's syndrome) while arterial thromboses can produce digital ischemia, renal infarction, or stroke. Arterial ischemia can also be due to embolization from nonbacterial thrombotic (marantic) endocarditis
Disseminated intravascular coagulation DIAGNOSIS Acute DIC suggested by clinical presentation, moderate to severe thrombocytopenia (less than 100, 000/µL and the presence of microangiopathic changes on the peripheral blood smear confirmed demonstrate evidence of both thrombin generation and fibrinolysis Fibrin degradation product or D-dimer levels Measurement of D-dimer is more specific although somewhat less sensitive than a latex agglutination test for fibrin degradation products The method of choice is the enzyme-linked immunosorbent assay (ELISA)
Disseminated intravascular coagulation DIAGNOSIS Acute DIC • Prothrombin time VII, X, V, and prothrombin, which are the most frequently decreased clotting proteins in DIC • Activated partial thromboplastin time less sensitive than the PT to deficiencies of components of the common pathway • Plasma fibrinogen concentration usually low in acute decompensated DIC, but may be elevated as an acute phase reactant in certain conditions, including pregnancy a plasma fibrinogen of 200 mg/d. L, although within the normal range, may represent a significant decrease in a patient whose baseline level, because of underlying malignancy, sepsis, or inflammation, should be 800 mg/d. L. thrombin time and reptilase time which are usually prolonged due to hypofibrinogenemia and the presence of fibrin degradation products.
Disseminated intravascular coagulation DIAGNOSIS Acute DIC reduced levels of endogenous coagulation inhibitors such as antithrombin III (AT III), protein C, and protein S A marked reduction in AT III levels at the onset of septic shock may be a sensitive marker of unfavorable prognosis, presumably by permitting persistence of the procoagulant state soluble fibrin monomers are elevated in both DIC and pre-DIC with a high degree of sensitivity and specificity specific assays for soluble fibrin monomers are not generally available.
Disseminated intravascular coagulation DIAGNOSIS Chronic DIC the platelet count may be only moderately reduced, plasma fibrinogen is often normal or slightly elevated, and the PT and PTT may be within normal limits the diagnosis may be largely based upon evidence of microangiopathy on the peripheral blood smear and increased levels of FDPs and particularly, D-dimer.
Disseminated intravascular coagulation DIAGNOSIS Acute DIC in the presence of severe liver disease decreased synthesis of coagulation factors and inhibitors, and thrombocytopenia may be induced by hypersplenism. liver disease alone may be associated with chronic or intermittent fibrinolysis, fibrinogenolysis, and elevated levels of FDPs. DIC versus TTP-HUS DIC versus primary fibrinolysis Primary fibrinolysis occurs when plasmin is generated in the absence of thrombosis direct infusion of thrombolytic agents prostate cancer surgery It can be distinguished from DIC by the absence of elevated level of D-dimers
Скачать презентацию EVALUATION OF THE PATIENT WITH A POSSIBLE BLEEDING
c2c5b82b95d6d2abb726a841c3706516.ppt