DVT and PE
(Q1) What Solid tumors are associated with a *higher incidence of VTE*? (Q2) Do mucin or non-mucin tumors cause an increase in coagulability? (Q3) Substance with procoagulant activity fall into two major categories?
(A1) *pancreatic CA, brain tumors, Stage III / IV CA* (A2) Early reports of *mucin -secreting adenocarcinomas* of GI tract (unable to purify a unique procoagulant moiety from mucin yet). Many *non- mucin tumors* ass. w/ hypercoagulability. (A3) TF-like procoagulant & cancer procoagulant
*(Q1)* What increases risk *VTE*? *(Q2)* Up to 1/2 of patients with a 1st episode of VTE have ____ and are described as having *unprovoked idiopathic VTE* (thrombophilla)-protein C/S anti-thrombin deficiency *NOTES:* - DVT + PE = VTE → 3rd most common cause of CVD
*(A1) RISK FACTORS:* *(1)* M > W (increase in age-esp. 80 yoa) *(2)* higher in white (over AA & His.) *(3)* 1/3 of pts w/ symptomatic VTE presents w/ PE (SOB) *(4)* 2/3 presents w/ DVT sx alone but have clinically silent PE *(A2)* no identifiable risk factors - the other 1/2 develop VTE secondary to well recognized, transient RF (long airplane ride, or recovering surgery)
Describe the difference in the Acute vs chronic changes in PE?
*Acute:* (1) *if pulm vascular bed <50% obstruction* → *RV maintains output* & BP normal (2) *if pulm vascular bed >50% obstruction* →*↑↑ pulm pressure (55 mmHg)* → ↑↑RV afterload and *no time for RVH* → *RHF* → hypotension → sudden death *Chronic:* -- *multiple PE over long period* allows *RV to adapt* to PHTN = *RVH* → *worsening dyspnea*→ *LV maintains CO* and no hypotension.
Review *Physiologic antithrombic mechanisms*:
*Antithrombin (AT)* = major protease inhibitor of the coagulation system *Protein C and its cofactor protein S (PC/PS)* → destroying factors Va and VIIIa *Tissue factor pathway inhibitor (TFPI)* → specifically quenches tissue factor-induced coagulation *Fibrinolytic system:* plasminogen, plasminogen activator (PA), and plasmin
Key features of *Massive PE* -Extensive Thrombosis *Makes up least # of cases* where as the *low-risk PE* has an excellent prognosis & makes up 3/4 of all PE cases
*B/L lung involvement* with multiple emboli and *massive saddle embolism*
Review *DVT* Prediction Rule: (9) - *NOTES:* cat scratch = cellulitis; an example of an alternative diagnosis *DVT WORK UP:* - what is the difference between low, moderate and high risk?
*DVT WORK UP:* (1) *low* risk: DVT score = *0* (5% chance) (2) *moderate* risk: " " = *1-2* (17% chance) - low / moderate risk do *d-dimers test* is sensitive NOT specific - (3) *high* risk: " " *> 2* - imaging via *compressible ultrasound* *NOTES:* -compressible US inconclusive - CT / MRI = very rare
What type of thrombus is more likely to cause a pulmonary embolism; *(deep venous* OR *superficial thrombophlebitis)* and why?
*DVT:* - blood clot in deep vein; predominately in the legs & thighs *NOTES:* - *Superficial thrombophlebitis*: thrombosis and inflammation of superficial veins *(varicose veins)* - provided the SVT has not extended into the deep veins, affected pts are at *negligible risks for PE*
Describe *VTE prophylaxis* (prevention):
*Early Ambulation* after surgery or *Unfractionated Heparin or Low Molecular Weight Heparin* in hospital if not ambulating *NOTES:* - *ambulation* = a technique of postoperative care in which a patient gets out of bed and engages in light activity
How do *endothelial cells* contribute to hypercoagulability?
*Endothelial cells may become procoagulant* under *TNF & IL-1* *TNF and IL-1 increase:* 1) *leukocyte adhesion* 2) *platlet activating* factor 3) *TF* (III) *TNF diminishes activation of Protein C:* 1) *downregulating thrombomodulin* expression 2) *suppressing endothelial fibrinolytic* activity 3) *increasing prod of IL-1*- *vicious cycle*
*Review:* What is the most common cause of inherited thrombophilia (hypercoagulability) in caucasians?
*Factor V Leiden point mutation (ARG →GLU)* - *homozygous* highest risk - *resistant* to action of Activated *protein C* *NOTES:* - APC normal function is to cleave Factor V & VIII - thrombotic risk increases with age & oral contraceptive (OCP) or hormone replacement therapy
*HYA:* What is the PE probability criteria?
*HAD CLOTS* - if a person doesn't come in with any of the HAD CLOTS r/o PE ( but if have one goes to the *Wells score*) *NOTES:* - estrogen = birth control - hemoptysis = coughing blood
*Pathophysiology of Venous pulmonary embolism (VTE):* Blood clot forms in the where? What are the consequences? (4)
*Location:* Blood clot forms in the *LE and migrates to the lung* *Consequences:* (1) *LE edema* & pain (2) *Respiratory:* = Hypoxemia (VQ mismatch) → pulm infarction, (3) *Cardiac* ↑PVR(PHTN) → ↑ RV strian / failure (4) *large clot*
CXR - usually normal, but can see *focal oligemia (Westermark's sign)* or *Hampton's hump* from a pulmonary infarction.
*NOTES:* - *Westermark sign* = dilation of pulmonary vessels proximal to embolism along with collapse of distal vessels often with a sharp cut off -*Hampton's Hump* = Pleural based parenchymal infarct - Wedge-shaped consolidation
Review Normal Venous Doppler
*NOTES:* - see that in the 2nd photo that the vein is compressed - indicates there is no clot (clots don't allow to fully compress)
Key features of *sub-massive PE* - about 1/4 of all PE cases
*RV dysfunction* despite normal systemic atrial pressure
Key features of *UE DVT:* (2) - less common than LE DVT
*Usually seen in cancer pts.* Most result from *indwelling lines* (pacermaker, defib, central lines- axillary and subclavian vv, catheter) *Paget-schroetter syndrome:* unprovoked DVT of dominant arm from strenuous effort
Pathophysiology of *Thromboembolic disease*: HINT: *SHE* Describe the process of platelets in making a clot:
*Virchow's triad* (SHE) (1) *S*tasis ( alterations in BF) (2) vascular *E*ndothelial injury (dysfunction) (3) *H*ypercoagulability (inherited or acquired) - Will have the *recruitment of platelets* that *release microparticles* → proinflammatroy mediators bind *PMN* and forms web-like networks/ platelet aggregation & thrombin generation
Most common EKG pattern in PE pts? - what else is seen?-
-- *Sinus tachycardia* (44%) (uncommonly S1Q3T3)
What makes *Peripheral PE* less likely to cause *pulmonary infraction*? Seen in pre-existing conditions like COPD / HF that have compromised oxygenation:
Circulation to the lungs arise from both pulmonary & bronchial arteries
Treatments of *Massive PE*?
Fibrinolysis with tissue plasminogen activator (tPA)
Many patients with *cancer are in a hypercoagulable state*: Why? (3) - will see *abnormal coagulation tests and DVT & PE*
Intact *tumor cells may express procoagulant activity* (+ thrombin) *Normal host tissue* will respond and express procoagulant activity in response to the tumor. *Cormbid RF of CA pts:* bed rest, Sx, drugs increase chance of coagulation
The most common Dx testing for PE? What other exams can one do? (2)
Most Common: CT Pulmonary Angiography (*CT PE protocol*) Other: (1) *Ventilation-Perfusion Scan (VQ scan)* -pic- - high suspicion of PE with no abnormalities on CXR (renal pts) (2) *Pulmonary Angiography* (very rare now)
*Pulmonary Embolism:* -Blockage of blood flow through a _____ usually arising from a blood clot in a deep vein of the leg (venous thromboembolism). -*Non-thrombotic material* also can cause an embolism in the lungs: *What is FATBAT?* *NOTES:* - Review definitions on slide (its an LO)
Pulmonary artery *FATBAT:* - *FAT* ( long bone fractures) - *Air*(NO2; bubbles - ascending drivers) - *Tumor cells* - *Bacteria* - *Amniotic fluid* (DIC, postpartum) - *Talc in IV drug use*
Key features of *LE DVT:* (2) - more common than UE DVT
The exact cause unknown *begins in calf* and goes proximal (popliteal / femoral veins) *Responsible for 90% or more of PE*
Where do *majority of thrombi occur in pregnancy*?
iliofemoral veins (deep veins of LLE) *NOTES:* -90% thrombi occur in deep veins of LLE (left more than right - b/c Left vein has more travel to the heart) - *left iliac vein compressd via fetus* (obstruction site is where the R iliac artery crosses the left iliac vein)