6Physical Examination Vital signs : T 38.2 C, PR 100 bpm, RR 20/min, BP 103/65 mmHg, SpO2 94% RAGA : Good consciousness, no tachypnea, not pale, no jaundice, no sign of chronic liver disease, no clubbing of fingersSKIN : petechiae at both legs, no ecchymosisno malar rash, no escharHEENT : no oral ulcer, no OC or OHL, no bleeding per gumLymph nodes : no superficial lymphadenopathy
7Physical ExaminationCVS: JVP 4 cm above sternal angle, no heaving, no thrill, normal S1S2, no murmurRS: trachea in midline, coarse crepitation and decreased breath sound LLLAbdomen: soft, not tender, no hepatosplenomegaly, shifting dullness negativeNS: WNL
8Physical Examination Extremities: Left calf swelling with tenderness, warmth, mild ill-defined erythemaCircumference leg Rt Lt cmThigh Rt Lt cmHoman’s sign positive Lt legPulse FA , PA , DPA 2+ bilaterallycapillary refill <2 seconds
9Problem list Male 36 yr ไข้ ไอ จุดเลือดออก ขาซ้ายบวม Fever for 10 days Cough, non-massive hemoptysis, left pleuritic chest pain for 10 days, and desaturationPetechiae both legs 3 daysLeft calf swelling and tenderness 3 days
10Problem list Male 36 yr ไข้ ไอ จุดเลือดออก ขาซ้ายบวม Fever for 10 days Cough, non-massive hemoptysis. pleuritic chest pain for 10 days, and desaturationPetechiae both legs 3 daysLeft calf swelling and tenderness 3 daysInfectiousNon infectious
11Male 36 yr ไข้ ไอ จุดเลือดออก ขาซ้ายบวม InfectiousSystemic infectionRickettsial infectionLeptospirosisDengue infectionPulmonary infectionBacterial pneumoniaPulmonary tuberculosisNon infectiousPulmonary embolism with left leg DVT
21Problem list Male 36 yr ไข้ ไอ จุดเลือดออก ขาซ้ายบวม Fever for 10 daysCough ,non massive hemoptysis for 10 daysThrombocytopeniaLeft femoropopliteal vein thrombosisIntermittent fever for 10 daysCough ,non massive hemoptysis for 10 daysPetechiae both legs 3 daysLeft leg swelling 3 daysInfectiousNon infectious : PE?Antiphospholipid syndromeMalignancy – solid/lymphoma with thrombocytopeniaInfectionthrombocytopenia////DVT
22Admit 5/8/53 Investigation Result Initial management Infectious H/C x2 sppsSputum GS CSSputum mycobacteriaDengue IgG IgMIFA O tsutsugamushiR typhileptospirosisPendingเก็บไม่ได้Ceftriaxone2 g v ODDoxycycline(100)1 tab o bid pcNon infectiousPE?DVTHypercoagulable?PT aPTTLupus anticoagulantAnti B2 GP1 IgGIgMAnticardiolipin IgGIgMHeparin ?Platelet 18000?ThrombocytopeniaPeripheral destruction/marrow diseaseConsult hematoSTE inII ,III,aVF, cardiac enzyme no risingConsult cardiologist22
23Admit 5/8/53 Investigation Result Initial management Infectious H/C x2 sppsSputum GS CSSputum mycobacteriaDengue IgG IgMIFA O tsutsugamushiR typhileptospirosisPendingเก็บไม่ได้Ceftriaxone2 g v ODDoxycycline(100)1 tab o bid pcNon infectiousPE?DVTHypercoagulable?PT aPTTLupus anticoagulantAnti B2 GP1 IgGIgMAnticardiolipin IgGIgMHeparin ?Platelet 18000?ThrombocytopeniaPeripheral destruction/marrow diseaseConsult hematoSTE inII ,III,aVF, cardiac enzyme no risingConsult cardiologist23
27Investigation PE non high risk D-dimer-not recommended in high clinical probability normal result does not safely excludeHigh-probability ventilation–perfusion lung scintigraphy confirms PE (I, level A)SDCT or MDCT showing a segmental or more proximal thrombus confirms PE (I, level A)European Heart Journal (2008) 29, 2276–2315
29VQ scan vs CTA CTA Advantage over VQ scan SpeedCharacterization of nonvascular structures,Detection of venous thrombosis.Caution in renal insufficiency,Ventilation–perfusion scanDiagnosis PE - high probability VQ scan inclinical probability intermediate to highFalse positive VQ scan*Prior pulmonary embolismUnderlying cardiopulmonary disease10% of smokers may have perfusion defect.N Engl J Med 2008*Prog Cardiovasc Dis. 1994
33Problem list Male 36 yr ไข้ ไอ จุดเลือดออก ขาซ้ายบวม Fever for 10 days Cough, non massive hemoptysis for 10 daysLeft femoropopliteal vein thrombosisThrombocytopeniaPulmonary embolism with DVT
34Management of PEAnticoagulation without delay - high or intermediate clinical probability of PE while workup (I, C)LMWH or fondaparinux - recommended initial Rx for most patients with non-high-risk PE (I, A)Unfractionated heparin (I, C)-High risk of bleeding- Severe renal dysfunctionEuropean Heart Journal (2008) 29, 2276–2315
35? Patient Data --Thrombocytopenia???? Early Anticoagulation Is Associated With Reduced Mortality for Acute PE? Patient Data --Thrombocytopenia????Chest 2010;137;
36PE …Thrombocytopenia Male 36 yr ไข้ ไอ จุดเลือดออก ขาซ้ายบวม ทีมแพทย์ Risk-benefit and TimeanticoagulantFurther inv and Rxthrombocytopeniaทีมแพทย์ผู้ปวยญาติ
37DDx VTE and Thrombocytopenia Anti-Phospholipid Syndrome- Primary- SecondaryMalignancy : Solid tumor , Lymphoma- hypercoagulable state VTE- thrombocytopenia BM involvement, 2o ITP, CMTParoxysmal nocturnal hemoglobinuriaHeparin-induced thrombocytopenia/thrombosis (HITT)Two diagnoses eg,- VTE: Hereditary Hypercoagulable Disease eg, Protein C def , Protein S def, Antithrombin def- Thrombocytopenia: ITP, infection, drug, etc.
38Progress and managment CTA pulmonary & CTV both legsWork up : hypercoagulable state-Lupus anticoagulant-anti-cardiolipin Ab-anti-β2GP I Ab-Protein C,Protein S-anti-thrombin IIICeftriaxone 2 gm iv O.D.Doxycycline(100)1x2 pcParacetamal(500) 2 tab prn for fever q 4-6 hrs
39Differential Diagnosis ThrombocytopeniaPeripheral destruction1° or 2 °ITP ,DIC- Marrow Disease
40Heparin iv in thrombocytopenia Keep APTT ratioKeep Plt > 50,000 mm3F/U Clinical bleeding/hemoptysis , CBCProtamine sulfate in hand
50Diagnosis Anti-phospholipid syndrome with ITP Pulmonary embolism and DVTImmune thrombocytopeniaAnti-phospholipid syndrome with ITP
51Revised Classification Criteria for the Antiphospholipid Syndrome At least one of the Clinical criteriaAt least one of the Laboratory criteriaMiyakis S, J Thromb Haemost 2006; 4: 295–306.
52Clinical Criteria Vascular thrombosis Pregnancy morbidity arterial, venous, or small vessel thrombosis, in any tissue or organFor histopathologic confirmation, thrombosis should be present without significant evidence of inflammation in the vessel wallPregnancy morbidityMiyakis S, J Thromb Haemost 2006; 4: 295–306.
53Clinical Criteria Vascular thrombosis Pregnancy morbidity >1 unexplained fetal death (GA >10 wk)>1 premature birth (GA <34 wk) due to (i) eclampsia or severe preeclampsia or (ii) placental insufficiency>3 unexplained consecutive spontaneous Abortions (GA <10 wk)Miyakis S, J Thromb Haemost 2006; 4: 295–306.
54Laboratory criteria** Anticardiolipin (aCL) antibody : IgG and/or IgM in medium or high titer (i.e. >40 GPL or MPL, or >99th percentile)Anti-2 glycoprotein-I antibody : IgG and/or IgM (>99th percentile)** > 2 occasions at least 12 wk. apartMiyakis S, J Thromb Haemost 2006;4:295–306.
55LA correlates better with thrombosis than aCL Giannakopoulos B, et al. Blood 2009;113:985-94
56Features associated with APS (non-criteria features of APS) Heart valve diseaseLivedo reticularisThrombocytopeniaNephropathyNeurological manifestationIgA aCLIgA anti-2 glycoprotein-IAntiphosphatidylserine AbAntiphosphatidylethanolamine AbAb against prothrombin aloneAb against phosphatidylserine/prothrombin complex- MR/MS/AR/AS; Valve thickness >3 mm, Localized thickening involving the leaflet’s proximal or middle portion, Irregular nodules on the atrial face of the edge of the mitral valve, and/or the vascular face of the aortic valve.- In unselected APS patients, LR has been retrospectively correlated with aCL and arterial thrombosis, but not with anti-b2GPI or LA, venous thrombosis, or pregnancy morbidity- The committee consented that thrombocytopenia occurring in patients with persistent aPL, in the absence of clinical manifestations of APS, should be considered to be different from ITP: such patients have an increased thrombotic risk and require closer follow-up.- Thrombotic microangiopathy involving both arterioles and glomerular capillaries; Fibrous intimal hyperplasia involving organized thrombi with or without recanalization, Fibrous and/or fibrocellular occlusions of arteries and arterioles, Focal cortical atrophy, Tubular thyroidization (large zones of atrophic tubules containingeosinophilic casts)- In one small study of APS patients without SLE, long-term presence of LA is a risk factor for dementia (Evidence Level II). In SLE patients, persistent elevation of aPL is associated with cognitive dysfunction (Evidence Level I). Transverse myelopathy (TM) is a rare entity within APS. Limited data suggest that in the 1% of SLE patients who manifest TM, the latter is associated with aPL (Evidence Level IV)The IgA aCL are usually detected together with either IgG and/or IgM isotypes in patients with APS. In patients with collagen disease, IgA aCL associates with thrombocytopenia, skin ulcers and vasculitis, indicating a patient subgroup at risk for specific clinical manifestations (Evidence Level III), and it is highly prevalent in African–American SLE patients.IgA anti-b2GPI are the most frequently detected antibodies in patients in specific ethnic groups.A systematic review on antiprothrombin antibodies and risk of thrombosis in APS failed to reveal an association, irrespective of isotype, site and type of event, or presence of SLE. Both the sensitivity and specificity of aPS/PT are higher than those for aPT-A, whereas 95% of patients with aPS/PT are also LA positive, suggesting that aPS/PT can also serve as a confirmatory assay for LA (Evidence Level II); these results, however, only come from one study , and concerns regarding aPS/PT arise from multivalent antibody binding; the possibility of measuring antibodies against non-complexed phospholipids present in the sample needs to be excluded.Miyakis S, J Thromb Haemost 2006;4:295–306.
58Detection of Lupus Anticoagulant Antibodies by in Vitro Coagulation Assays The intrinsic coagulation pathway is initiated by contact activation on glass, silica, or kaolin (as in the activated partial-thromboplastin time [APTT], colloidal-silica clotting time [CSCT], and kaolin clotting time[KCT] assays), whereas the extrinsic coagulation pathway is initiated by the formation of a complex between tissue factor (TF) and factor VIIa (as in the dilute prothrombin time [dPT] assay).Russell’s viper venom directly activates factor X. Taipan, Textarin, and Ecarin snake-venom extracts directly activate prothrombin but have different cofactor requirements. Taipan venom activation of prothrombin requires phospholipid and calcium but not factor Va. Textarin activation of prothrombin requires phospholipid, calcium, and factor Va, whereas Ecarin activation of prothrombin is independent of cofactors and does not requirephospholipid, calcium, or factor Va.Levine JS. NEJM 2002;346:
59Lupus Anticoagulant Test Step 1 : Screening – Prolongation of coagulation in at least one phospholipid-dependent in vitro coagulation assay with the use of platelet-poor plasmaStep 2 : Mixing study with normal pooled plasma – failure to correct the prolonged coagulation timeStep 3 : Confirmation by shortening or correction of the prolonged coagulation time after the addition of excess phospholipid or platelets that have been frozen and then thawedStep 4 : Ruling out other coagulopathies with the use of specific factor assays if the confirmatory test is negative or if a specific factor inhibitor is suspected
60LA1 / LA2 Ratio = Screening / Confirm Ratio ( a/c : b/d ) Fig. 2. Clotting times obtained with an LA positive test plasma or normal plasma (NP) with a low PL concentration (screening test) and a high PL concentration (confirmatory procedure). The PL concentration used in the ‘‘usual’’ APTT is indicated. The Lupus Ratio (a/b:c/d) is mathematically identical with the screening/confirm ratio (a/c:b/d).
62A Meta-analysis Comparing LMWH – UFH in the Treatment of Venous Thromboembolism ARCH INTERN MED/VOL 160, JAN 24, 2000
630.47 (95% CI, ;P .06), but this did not reach statistical significance (Figure 4Risk for heparin-induced thrombocytopenia with LMWH –UFH thromboprophylaxis: a meta-analysisBLOOD, 15 OCTOBER VOLUME 106,
64Risk for heparin-induced thrombocytopenia with LMWH –UFH thromboprophylaxis: a meta-analysisBLOOD, 15 OCTOBER VOLUME 106,