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Vidu Bala Mokkala. Sohail Chaudhry.

Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

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Page 1: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

Vidu Bala Mokkala. Sohail Chaudhry.

Page 2: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal PTT and was referred to the hematology and oncology clinic for further evaluation.

PMH- HTN, Dyslipidemia, DM, Mild depression, Anxiety disorder.

PSH: Appendectomy, Cholecystectomy, Partial Hysterectomy for heavy menstrual cycles 30 yrs back.

Page 3: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

SH: Never smoked. Not an alcoholic. FH: No bleeding disorders in the family. Home medications:

Metformin,Januvia,Gemfibrozil,

Zetia,Crestor,MVT,Lotrel,Atenolol,Lexapro,Calcium and Vitamin D, Aspirin,Omeprazole.

Vitals: Stable. Physical examination-Negative.

 

Page 4: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

CBC- WBC-5.7, HGB-11.6,HCT-36.1,PLT-339. CMP-Normal. PT/INR-Normal. PTT-66.7.(Increased)

Page 5: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

Coagulation is a complex process by which blood forms clots. 

Disorders of coagulation can lead to an increased risk of bleeding(hemorrhage) or clotting(thrombosis).

Hemostasis is the process of blood clot formation at the site of vessel injury.

Platelets immediately form a plug at the site of injury and this primary hemostasis.

Secondary hemostasis occur simultaneously: proteins in the blood plasma, called coagulation factors or clotting factors, respond in a complex cascade to form fibrin strands which strengthen the platelet plug.

Page 6: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

Platelet Activation-collagen and thrombin.

Platelet Adhesion-platelet glycoprotein Ib-IX-V complex binding to the VWF in the subendothelial matrix.

Platelet Aggregation- via fibrinogen receptors/Glycoprotein IIB-IIIA receptors.

Platelet Secretion(Granules)-alpha and dense granules.

Fibrin plug formation.

Page 7: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal
Page 8: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal
Page 9: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

1.Cyclooxygenase inhibitors: Aspirin

2.Adenosine diphosphate (ADP) receptor inhibitors Clopidogrel (Plavix) Ticlopidine (Ticlid)

3.Phosphodiesterase inhibitors: Cilostazol(Pletal

4.Glycoprotein IIB/IIIA inhibitors (intravenous use only) Abciximab (ReoPro) Eptifibatide (Integrilin) Tirofiban (Aggrastat)

5.Adenosine reuptake inhibitors: Dipyridamole (Persantine)

Page 10: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal
Page 11: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal
Page 12: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal
Page 13: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

Vitamin K antagonists(Coumadin): Inhibits the vitamin K-dependent synthesis of biologically active forms of the calcium-dependent clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S.

Unfractionated Heparin(UFH): Binds to Antithrombin(AT) at the site of native pentasaccharide sequence, changing its conformation and converting it from slow to a rapid inactivator of several coagulation factors, particularly X a. In order to inactivate thrombin,heparin should bind to thrombin and AT simultaneously,an effect that occurs only when the molecule exceeds 18 monosaccharide units (greater than 6000 daltons). 

  Direct thrombin inhibitors(DTI): Univalent DTI'S (Argatroban and dabigatran)

and Divalent DTI'S (Hirudin,Lepirudin,Bivalirudin).

Page 14: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

Low Molecular Weight Heparin (ardeparin,certoparin,enoxaparin,nadroparin, reviparin,dalteparin, tinzaparin,parnaparin): Similar action as UFH. They have

lesser effect on thrombin than Xa because most of the molecules are not long enough to bind simultaneously with thrombin and AT.

  Synthetic pentasaccharide inhibitors of factor Xa (Fondaparinux and

Idraparinux): synthetic sugar composed of the five sugars (pentasaccharide) in heparin that bind to antithrombin. It is a smaller molecule than low molecular weight heparin.

Page 15: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal
Page 16: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal
Page 17: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

Etiology for prolonged PT with normal PTT: 

Inherited: Factor VII defeciency.

Acquired:1. Acquired factor VII deficiency2.  Vitamin K deficiency- biliary obstruction, malabsorption, cystic fibrosis,

resection of the small intestine,Certain antibiotics (particularly some cephalosporins and other broad-spectrum antibiotics), salicylates, megadoses of vitamin E, and hepatic insufficiency, coumadin.

3.  Liver disease4. Coumadin administration 5. Inhibitor of factor VII.

Page 18: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

Etiology for prolonged PTT with normal PT:

Inherited1. Deficiency of factors VIII, IX, or XI 2. Deficiency of factor XII, prekallikrein, or HMW kininogen-Not associated

with a bleeding diathesis. 3. von Willebrand disease 

Acquired1. Heparin administration2. Inhibitor of factors VIII, IX, XI, or XII3. Acquired von Willebrand disease4. Lupus anticoagulant-associated with thrombosis, rather than bleeding

Page 19: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

Etiology of elevated PTT and PT:

Inherited1. Deficiency of prothrombin, fibrinogen or factors V or X2. Combined factor deficiencies  Acquired1. Liver disease2. Disseminated intravascular coagulation3. Supratherapeutic doses of heparin4. Supratherapeutic doses of coumadin5. Combined heparin and coumadin administration6. Combined argatoban and coumadin administration7. Inhibitor of prothrombin, fibrinogen or factors V or X8. Primary amyloidosis-associated factor X deficiency

Page 20: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

1. APTT -83.0 (22.3-37.8)2. APTT 1:1 mixing studies-46.2 (22.3-37.8)3. BT-3.5 (2.3-9.5)4. Factor XII activity-140 (50-150)5. Factor XI activity -175 (65-150)6. Factor IX activity -188 (60-166)7. Factor VIII activity-221 (50-180),inhibitor negative8. Factor V activity   -152 (>50 IU/DL),inhibitors are not tested when activity

of Factor V is (>50 IU/DL)9. Lupus anticoagulant- undected.10. Cardiolipin Ab. -negative (IGG and IGM-<10)11. Platelet Function Studies:Collagen/Epinephrine closure time-107.12. Beta 2 glycoprotein antibody –negtive.

13. VWF comprehensive screen-Negative. 

Page 21: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

•After an abnormality in a clotting test (PT/PTT)has been detected, it is important to differentiate between a clotting factor deficiency and an inhibitor (an antibody or other interfering substance directed against the clotting factor).

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 clotting test returns to normal after a 1:1 dilution with normal pooled plasma, a factor deficiency was the cause of the abnormal test.

Page 22: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

•Most agents which inhibit clotting factor activity (such as antibodies) will not be effectively diluted out after addition of an equal volume of normal pooled plasma. 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 at 37ºC may resolve this issue. As an example, delayed reactivity is characteristic of factor VIII inhibitors.

•If the 1:1 dilution corrects the abnormal test, the deficient factor(s) can be determined by individual clotting factor assays.

Page 23: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

If the test is not corrected by dilution, the most common inhibiting factors are:

•Heparin in the sample

•Antiphospholipid antibodies; these are more commonly associated with a hypercoagulable state rather than bleeding.

•Inhibitors directed against factors VIII, IX, or X. These inhibitors can be associated with life-threatening bleeding and require urgent attention by a hematologist and the involved laboratory. 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 D-dimer).

•Inhibitors to other factors. These are less common and are detected by individual factor assays.

Page 24: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal

A first step in evaluating an isolated prolonged aPTT or TT is to exclude heparin as the etiology. 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. Alternatively, one can use one of the following two methods:

Reptilase time method: perform a thrombin time (TT) and reptilase time (RT). Heparin is present if the TT is prolonged and the RT is normal. Reptilase, a thrombin-like enzyme obtained from snake venom, differs from thrombin by resisting inhibition by heparin via antithrombin III.

Heparin reversal method: if a prolonged TT is normalized after the addition of protamine a commercially available ion exchange resin which absorbs heparin in the sample (Heparsorb), or a heparinase (Hepzyme), heparin or a heparin-like material is present.

Page 25: Vidu Bala Mokkala. Sohail Chaudhry.. 59 year old female was seen by the PCP for pre-op evaluation for septoplasty and was found to have incidental abnormal