Kembara Xtra - Medicine - Pulmonary Embolism

Kembara Xtra - Medicine - Pulmonary Embolism 
​Due to the significant early fatality rates associated with pulmonary embolism (PE), which is an acute cardiovascular condition, immediate medical attention is needed. The most severe form of venous thromboembolism (VTE), PE results in acute right ventricular failure and pulmonary vascular bed blockage, both of which are life-threatening conditions.
According to severity, PE is divided into three categories: Low-risk PE, which is acute and devoid of clinical indicators of a poor prognosis; Submassive PE, which lacks systemic hypotension but exhibits either myocardial necrosis (elevated troponin); or right ventricle dysfunction (RV dilation or systolic dysfunction on echocardiography [echo], RV/LV ratio >1 on computed tomography [CT], elevation of B-type

Epidemiology 
Case mortality rates range greatly (from 1-60%); at two weeks, they are roughly 11%.
About 100,000 occurrences per year in the United States; incidence ranges from 30 to 80 per 100,000; incidence is higher in African Americans and lower in Asians; incidence rises with age, with the majority of cases occurring in people between the ages of 60 and 70.
 1:1,000 pregnancies (including postpartum) Prevalence Epidemiology is challenging to determine outside of the hospital setting because some patients with PE may remain asymptomatic, the first presentation of PE can be sudden death, or the diagnosis of PE is incidental. 250,000 hospitalizations per year in the United States, 10-60% in hospitalized patients. Highest risk for orthopedic and cancer patients.
Between 2012 and 2014, the prevalence of PE among hospitalized adults who were treated for their first episode of syncope was 17.3%. among Asian nations (China, India, Japan, Korea, Singapore), the prevalence of PE ranged from 2.5 to 23 per 10,000 patients.

Pathophysiology and Etiology 
Thrombus is brought on by endothelial injury, venous stasis, and modifications to the coagulation process.
 Leads to decreased pulmonary compliance, poor gas exchange, and increased pulmonary vascular resistance. Typically, the main cause of mortality is RV failure brought on by pressure overload.
Proximal lower extremity deep vein thrombosis (DVT) is the most frequent cause of PE (85%).
Genetics: Leiden is the most prevalent form of thrombophilia. Prothrombin G20210A: 3% of Caucasians; rare in African American, Asian, and Native American; 6% in patients with VTE; and, infrequently, deficits in protein C, S, and antithrombin. +5.5% in Caucasian, 2.2% in Hispanics, 1.2% in African American, and 0.5% in Asian; related with 20% of VTE.

Risk Elements 
Oral contraceptives are the most common risk factor for women, followed by advanced age, obesity, extended immobility, surgery, significant trauma, joint replacement, spinal cord injury, cancer, hormone replacement treatment, pregnancy/puerperium, prior thrombosis, antiphospholipid syndrome, and heredity.

Prevention 
The use of thromboprophylaxis in COVID-19 infection is uncommon but may be considered in patients at high risk (previous VTE, recent surgery, limb immobilization, recent trauma, etc.). Low VTE risk measures include early postoperative ambulation, compression stockings, and intermittent pneumatic compression.
In order to prevent VTE after hip or knee replacement surgery, patients should take low-molecular-weight heparin (LMWH), fondaparinux, apixaban, dabigatran, rivaroxaban, or low-dose unfractionated heparin (UFH) for 10 or more days. In order to prevent VTE after spinal cord injury, hip fracture surgery, and trauma surgery, patients should take vitamin K antagonists (VKA) for 28 to 35 days.

Accompanying Conditions 
the COVID-19 virus

Diagnosis 
Create a pretest probability using clinical standards.
Clinical symptoms of DVT are present with a Wells score of +3, and an alternative diagnosis is less likely than PE.
D-dimer has a very high negative predictive value (NPV), so if it is less than 500 ng/mL, PE is ruled out. Interpretation: 2 points, low probability (obtain D-dimer); 2 to 4 points, moderate probability (obtain D-dimer but consider initiating anticoagulation); >4 points, high probability (obtain spiral CT angiogram if patient is stable and initiate anticoagulation.
Determine whether the presentation is idiopathic or provoked. Wells score: Each predictor is +1; PE unlikely if 0 to 1, PE likely if >2; Geneva score: Each predictor is +1 except for heart rate >95 beats/min, which is +2.
About 30% of cases progress without a clear risk factor.
Bleeding risk (prior anticoagulation, bleeding history, recent interventions/surgeries, liver illness, kidney disease) Sudden onset dyspnea (>85%), chest pain (>50%), cough (20%), syncope (14%), and hemoptysis (7%).

clinical assessment 
Dyspnea, syncope, hemoptysis, tachycardia, tachypnea, pronounced S2, pleuritic chest discomfort, pleural friction rub, rales, visible collateral veins in the legs, signs of DVT, and jugular vein distention, S3 or S4, systolic murmur at the left sternal border, and hepatomegaly, signs of RV failure

Multiple Diagnoses 
Cardiac/vascular: myocardial infarction, pericarditis, congestive heart failure, aortic dissection; Pulmonary: pneumonia, bronchitis, pneumothorax, pneumonitis, chronic obstructive pulmonary disease exacerbation; Musculoskeletal: rib fracture(s), chest wall discomfort

Laboratory Results 
D-dimer ELISA: If it is negative (high NPV) in patients with low pretest likelihood, it can rule out PE. If positive, it is not diagnostic (low positive predictive value [PPV]), and it is useless if the pretest likelihood is high or intermediate.
Consider hypercoagulable tests in young patients with idiopathic, recurrent, or significant family history of VTE. CBC, creatinine, aPTT and PT, and ABG.
- In the acute context, do not test for protein C, S, factor VIII, or antithrombin.
- Patients with elevated D-dimer levels and intermediate or high pretest probabilities require additional diagnostic testing.
● Chest x-ray (CXR): Westermark sign (lack of vessels in an area distal to the embolus), Hampton hump (wedgeshaped opacity with base in pleura), Fleischner sign (enlarged pulmonary arteries), pleural effusion, hemidiaphragm elevation ● ECG: right heart strain, S1Q3T3 ● CT pulmonary angiography: sensitivity 96-100%, specificity 86-89%; NPV 99.8%. If normal, it rules out PE if the clinical likelihood is low or moderate.
Use ventilation/perfusion scintigraphy (V/Q scan) in the absence of or when CT angiography is not appropriate. PE is diagnosed with a high-probability V/Q scan; a normal V/Q scan excludes PE.
Echo: evaluates RV function and thrombus in transit; Magnetic resonance (MR) angiography: less sensitive and specific than CT angiography; Compression venous ultrasound (CUS): noninvasive. Pulmonary angiography: gold standard invasive and technically challenging.
Specificity 95%, sensitivity >90%. In patients who have a clinical suspicion of having PE, it validates the diagnosis.
While awaiting results, begin therapy if preclinical probability is intermediate or high and the patient has a low risk of bleeding. CT venography can be performed concurrently with CT angiography and boosts diagnostic yield.
Initial Tests (Laboratory and Imaging) Labs: CBC: for anemia, thrombocytosis, and leukocytosis; CMP: to check for electrolyte abnormalities; D-dimer: *used to rule out DVT/PE when clinical suspicion for PE is low to moderate; BNP: to rule-out congestive heart failure as a cause; Troponins: Rule out myocardial causes.
Imaging: If the CXR is normal but there is hypoxemia, PE is suspected.
- Venous Doppler: initial DVT test; positive venous Doppler with tachypnea and SOB can start PE treatment.

Tests in the Future & Special Considerations
Diagnostic Procedures/Other Pulmonary Angiography-Definitive Test Test Interpretation D-dimer (performed if Wells criteria for PE is less than or equal to 4) - Normal: PE is ruled-out.
Move on to imaging (spiral CTA) if the level is high.
Spiral CTA - Diagnostic/positive: Treat for PE (done if Wells is >4 or D-dimer is high).
- Nondiagnostic/inadvisable: Run a V/Q scan and a CUS.
When a V/Q scan or CUS is negative, a TEE, MR, or pulmonary angiography is positive, and PE is treated.

Management 
Risk classification is the foundation of treatment.
Low-risk PE: Use an inferior vena cava (IVC) filter or anticoagulation.
Massive PE anticoagulation + definite INR consult for thrombolysis/embolectomy catheter/surgery Submassive PE anticoagulation + potential INR-guided thrombolysis
goal is to keep SaO2 over 92%

Medication 
Start your initial therapy for the first 5 to 10 days with LMWH, fondaparinux, and UFH. When the INR reaches 2 to 3 for 24 hours, VKA can be begun on the first day and must overlap with parenteral therapy for at least five days.
It is also permitted to provide dabigatran or edoxaban after 5 to 10 days of parenteral therapy.
rivaroxaban or apixaban are oral options for both initial and ongoing treatment.
Patients with significant PE and low risk of bleeding should think about taking systemic thrombolytics if there are no contraindications.
First Line ● UFH: – IV bolus of 80 U/kg or 5,000 U followed by continuous infusion (initially 18 U/kg/hr or 1,300 U/hr) with dose adjustments to maintain aPTT that corresponds to anti- Xa levels of 0.3 to 0.7 – SC injection: two options: ○ Monitored: 17,500 U or 250 U/kg BID with dose adjustments to maintain an aPTT that corresponds to anti-Xa levels of 0.3 to 0.7 measured 6 hours after a dose ○ Fixed dose: 333 U/kg initial dose, followed by 250 U/kg BID ● LMWH: preferred due to lower risk of major bleeding and heparin-induced thrombocytopenia (HIT) – Enoxaparin (Lovenox) 1 mg/kg/dose SC q12h – Dalteparin (Fragmin) 200 U/kg SC q24h – Fondaparinux (Arixtra) 5 mg (body weight <50 kg), 7.5 mg (body weight 50 to 100 kg), or 10 mg (body weight >100 kg) SC q24h ● Maintenance therapy: warfarin on day 1, if possible; 5 mg/day for 3 days in hospitalized or older patients and at a dose of 10 mg in <60 years of aged patients; adjust dose to maintain an INR of 2 to 3; needs to overlap with UFH, LMWH, or fondaparinux: 5 to 7 days, until 2 consecutive days of therapeutic INR ● Rivaroxaban: 15 mg BID × 3 weeks and then 20 mg once daily to complete treatment. It is safe to use in HIT and less likely to cause serious bleeding side effects than warfarin. Edoxaban: 60 mg once daily (reduced to 30 mg once daily if CrCl 30 to 50 mL/min or body weight 60 kg). Prior to beginning edoxaban, patients must first get LMWH medication for at least five days. Apixaban: 10 mg BID for 7 days, then 5 mg once daily; less major bleeding episodes; okay to use in HIT; Dabigatran: requires initial treatment with LMWH; okay to use in HIT ALERT; Contraindications: - Active bleeding - Heparin: HIT - LMWH: HIT, renal failure - Warfarin: pregnancy - Rivaroxaban and fondaparinux Risk is increased by using dronedarone or ketoconazole.
Dabigatran, apixaban, or rivaroxaban do not require a dosage reduction plan to treat acute PE. Pregnancy considerations include the following: Warfarin is teratogenic; nursing is safe LMWH: Dalteparin, enoxaparin, and fondaparinux are Category B; heparin is Category C: Use only if the benefit justifies the risk.
Rivaroxaban is Category C for UFH: requires aPTT monitoring; can result in osteoporosis if administered for a long time.
Dabigatran is in Category C and is only used when the benefit outweighs the risk. Edoxaban and apixaban are in Category B and increase bleeding risk.

Next Line
Massive PE: Tissue plasminogen activator (tPA) 100 mg infused over 2 hours if hemodynamic compromise and low bleeding risk are present. Absolute contraindications: - Intracranial hemorrhage, intracranial cerebrovascular or malignancy, ischemic stroke within three months, possible aortic dissection, bleeding diathesis, active bleeding, recent neurosurgery, or major trauma

Surgical Techniques 
IVC filter implantation in cases of absolute anticoagulation contraindication or recurring PE despite sufficient anticoagulation therapy. Emergency embolectomy in cases of major PE with thrombolysis contraindications.
Consider submassive PE or US-assisted catheter-directed thrombolysis, both of which carry a medium risk of death.

Admission 
Patients in a selected, low-risk population with acute pulmonary embolism (PESI score class I or II) could be handled in an outpatient setting with close follow-up.
 If hemodynamically unstable, ICU-level care

Constant Care 
Duration of anticoagulation: Unprovoked PE >3 months; consider long-term or prolonged secondary prophylaxis if bleeding risk is low; Provoked PE (trigger no longer present) 3 months.
When a woman has their first unprovoked VTE, the HERDOO2 Score can be used to indicate how long she will need therapy. After six months, low risk patients (0 to 1 criterion) may safely discontinue treatment.
PE for cancer: LMWH for the first three to six months. As long as the patient has an active cancer, consider supplementary prophylaxis.
Recurrent PE without apparent cause: long-term anticoagulation

Take Action 
Consider knee-high compression stockings if there is concurrent DVT.
Patient Monitoring The ideal INR range is between 2 and 3.
aPTT must be observed in SC UFH.
If using LMWH in specific situations, such as pregnancy, younger patients, or renal disease, Anti-Xa can be evaluated.


Modification of Lifestyle 
Patients who are at risk for blood clots (such as those who are sedentary, recovering from surgery, pregnant, or have cancer) should get advice on precautions.

Prognosis 
PESI score predicts 30-day mortality: submassive 6-14%; massive PE 15-60%. Stratified by risk classes depending on number of risk factors: class I (very low mortality risk; 0-1.6%), class II (low mortality risk; 1.7-3.5%), class III (moderate mortality risk; 3.2-7.1%), class IV (high mortality risk; 4-11.4%), and class V (very high mortality risk; 10-24.5%) ● Any one of the following defines high risk: age >80 years, cancer, chronic cardiopulmonary disease, heart rate 110 beats/min, systolic blood pressure <100 mm Hg, O2 saturation <90%.
Low early mortality risk: no shock or hypotension, no sPESI; imaging is optional. High early mortality risk: shock or hypotension, plus sPESI >1 + RV dysfunction signs. Intermediate high early mortality risk: no shock or hypotension, plus sPESI >1 + RV dysfunction signs. Intermediate low early mortality risk: no shock or hypotension, plus sPESI >1 + either RV dysfunction by imaging or cardiac laboratory biomarkers.
Patients with active malignancy have a much greater mortality rate from PE (up to 47-fold higher).

Complications 
Dyspnea, altered pulmonary vasculature, and decreased exercise tolerance are among symptoms of post-PE syndrome.

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