DVT Deep venous thrombosis) ) By Dr- Hayam M. AL-moutary Supervised by Dr-Abdulla AL-goblain
Content   Epidemiology  Symptom& sign Risk factor Deferential diagnosis Diagnosis Management
DVT the formation of a thrombus in the deep veins of the leg Virchow triad  venous stasis vessel wall injury hypercoagulable state
Epidemiology  DVTs occur in about 1 per 1000 persons per year. 100,000 deaths may be directly or indirectly related to these diseases In  pregnant  women, it has an incidence of 0.5 to 7 per 1,000 pregnancies, and is the second most common cause of  maternal death  in developed countries after bleeding Journal of Internal Medicine volume 232 Issue 2, Pages 155 - 160
Risk factor General   Age  Immobilization longer than 3 days  Pregnancy and the postpartum period  Major surgery in previous 4 weeks  Long plane or car trips (>4 h) in previous 4 weeks Medical  Cancer  Previous DVT  Stroke Sepsis  Nephrotic syndrome  Ulcerative colitis SLE Protein c & s deficiency Obesity
Risk factor  Trauma  Multiple trauma Drugs/medications  OCP
In a five-year case-control study (1988 to 1993) at Assir Central   Hospital (ACH), Abha (8,000 feet above sea level), Saudi Arabia,   92 of 129 patients suspected of deep venous thrombosis (DVT)   were studied with ascending contrast venography (CV) (74 patients,   80.4%) or Doppler ultrasonography (DUS) (18 patients, 19.6%).   Female-to-male ratio was 2.3 to 1. Age range of patients was   twelve to ninety years; mean age was 44.45 yrs ±17.38   years. DVT hospital incidence was 18 per 10,000 admissions  Angiology, Vol. 46, No. 12, 1107-1113 (1995) http://ang.sagepub.com/cgi/content/abstract/46/12/1107
Most risk factor chronic diseases (21.7%), trauma and surgery (19.6%),  pregnancy and oral contraceptives usage (16.3%).  most  symptom and sig n tenderness (95.6%) Limb   swelling was noted in 93.5% of patients. Pulmonary embolism was the greatest complication
clinical feature swelling, principally unilateral,  Leg pain occurs in 50% of patients SOB  Clinical signs and symptoms of PE as the primary manifestation occur in 10% of patients with confirmed DVT In patients with angiographically proven PE, DVT is found in 45-70%.
clinical feature Unilateral edema Leg tenderness Redness, hotness Bluish discoloration Absent or decrease pulse
Clinical feature  Phlegmasia cerulea dolens   leg is cyanotic from massive ileofemoral venous obstruction.  The leg is usually markedly edematous, painful, and cyanotic. Petechiae are often present . Phlegmasia alba dolens Painful white inflammation was originally used to describe massive ileofemoral venous thrombosis and associated arterial spasm. The affected extremity is often pale with poor or even absent distal pulses
Phlegmasia cerulea dolens
Clinical feature  Superficial thrombophlebitis  is characterized by the finding of a palpable, indurate, cordlike, tender, subcutaneous venous segment.  40% of patients with superficial thrombophlebitis without coexisting varicose veins and with no other obvious etiology (eg, intravenous catheters, intravenous drug abuse, soft tissue injury) have an associated DVT
DVT
Deferential diagnosis Cellulitis, lymphangitis Lymphedema Postphlebitic syndrome Ruptured Baker cyst Varicose veins Superfical thrombophlibitis
( Diagnosis   ( work up History Physical examination(work up) Probablity  scoring (well score) Blood test D-dimar Other blood test Imaging study MRI , U/S , venography
Physical examination Homans' test  Dorsiflexion of foot elicits pain in posterior calf.   Warning : it must be noted that it is of little diagnostic value and is theoretically dangerous because of the possibility of dislodgement of loose clot. Pratt's sign : Squeezing of posterior calf elicits pain. back
Score (wells score)   Clinical Parameter Score +1 Active cancer (treatment ongoing, or within 6 mo or palliative) +1 Paralysis or recent plaster immobilization of the lower extremities +1 Recently bedridden for >3 d or major surgery <4 wk +1 Localized tenderness along the distribution of the deep venous system +1 Calf swelling >3 cm compared with the asymptomatic leg +1 Pitting edema (greater in the symptomatic leg) +1 Previous DVT documented +1 Collateral superficial veins (nonvaricose) -2 Alternative diagnosis (as likely or greater than that of DVT)
Wells score  Total of Above Score > 3 High probability 1 or 2 Moderate probability < 0 Low probability
case 35 year old female recently pregnant, now on OCP,  complain of 1 week unilateral right leg swelling , no history of trauma,  she has DVT history 2year ago On P/E her right calf is 5 cm greater in circumference than her left and there is tenderness when squeeze the gastroncemius muscle.
Blood test complete blood count Primary coagulation studies: PT, APTT,  INR renal function  test and electrolytes liver function test
investigation D-dimer testing   D-dimer antibodies account for their high sensitivity for venous thrombo embolism. D-dimer level may be elevated in any medical condition where clots form. D-dimer level is elevated in trauma, recent surgery, hemorrhage, cancer, and sepsis. The D-dimer assays have low specificity for DVT; therefore, they should only be used to rule out DVT, not to confirm the diagnosis of DVT .
D-dimer results should be used as follows :  A negative D-dimer assay result rules out DVT in patients with low-to-moderate risk and a Wells DVT score less than 2.  All patients with a positive D-dimer assay result and all patients with a moderate-to-high risk of DVT (Wells DVT score  > 2) require a diagnostic study (duplex ultrasonography).
Duplex ultrasonography Technological advances in ultrasonography have permitted the combination of real-time ultrasonographic imaging with Doppler flow studies (duplex ultrasonography). The absence of the normal phasic Doppler signals arising from the changes to venous flow provides indirect evidence of venous occlusion
Duplex ultrasonography
Duplex ultrasonography A dvantage  helpful to differentiate venous thrombosis from hematoma, Baker cyst, abscess, and other causes of leg pain and edema.  Disadvantage  Venous thrombi proximal to the inguinal ligament are also difficult to visualize  Nonoccluding thrombi  not be able to differentiate between old and new clots
MRI In the second and third trimester of pregnancy, MRI is more accurate than duplex ultrasonography because the gravid uterus alters Doppler venous flow characteristics.  In suspected calf vein thrombosis, MRI is more sensitive than any other noninvasive study.
MRI Disadvantage   Expansive lack of general availability technical issues limit its use
CT venography(gold stander) The  gold standard  is  intravenous venography , which involves injecting a peripheral vein of the affected limb with a contrast agent and taking CT, to reveal whether the venous supply has been obstructed. Because of its invasiveness, this test is rarely performed
CT venography(gold stander)  A number of small studies have compared CT venography alone to duplex ultrasonography alone for the diagnosis of lower extremity DVT.  Similar high sensitivities for ultrasonography and CT have been reported, but no large trials comparing the two have yet been performed
CT venography(gold stander) Disadvantage   visualized veins, artifactual interference from metal implants such as hip and knee arthroplasties . contraindications to the administration of contrast dye.
Bilatral thrombosis
High clinical pretest probability- DVT likely Doppler ultrasound Ultrasound positive for DVT Diagnoses of DVT confirmed Begin treatment   Ultrasound negative for DVT D-Dmer test (if available and reliable) Otherwise skip  to repeat ultrasound D-Dimer positive Repeat ultrasound in 1 week D-Dimer negative DVT ruled out   Repeat ultrasound positive for DVT Diagnoses of DVT confirmed Begin treatment Suspect DVT Low clinical pretest  probability- DVT likely Consider starting with D-dimer  test first  (if available and reliable ) Or skip to ultrasound D-dimer positive D-Dimer negative DVT ruled out Doppler ultrasound Ultrasound positive for DVT Diagnose of DVT confirmed  Begin treatment   Ultrasound negative for DVT DVT ruled out  (consider repeat  ultrasound if  D-dimer not available)
Complications of deep vein thrombosis  There are two main complications of deep vein thrombosis (DVT): pulmonary embolism  post-thrombotic syndrome occurs in 15% of patients with deep vein thrombosis (DVT). It presents with leg oedema, pain, nocturnal cramping, venous claudication, skin pigmentation, dermatitis and ulceratiaion (usually on the medial aspect of the lower leg).
management Non-pharmcological   we can reduce  risk of DVT by making changes to patient  lifestyle, such as: avoid smoking  eating a healthy balanced diet  getting regular exercise and  maintaining a healthy weight or losing weight if patient obese Rise leg , This reduces the pressure in the calf veins
Travelling drink enough amount of water  avoid taking sleeping pills as it can cause immobility perform simple leg exercises, such as regularly flexing ankles take occasional short walks when possible wear elastic compression stockings
Compression stockings  Elastic compression stockings should be routinely applied &quot;beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis  Most trials used knee-high stockings. A meta-analysis of  randomized controlled trials  by the  Cochrane Collaboration  showed reduced incidence of post-phlebitic syndrome.
Treatment  The current guidelines recommend short-term anticoagulation with LMWH SC ,   unfractionated heparin SC ,   (Grade 1A),  should continue for at least 5 days and until the INR is  > 2 for 24 hours (Grade 1C).  Warfarin 5 mg PO daily  is overlapped with heparin for 4-5 days until the international normalized ratio (INR) is therapeutically elevated to 2-3.  For the first episode of DVT, patients should be treated for 3-6 months. Recurrent episodes should be treated for at least 1 year [Guideline] American Academy of Family Physicians
Treatment  A protocol for IV heparin use is as follows: Give an initial bolus of 80 U/kg Initiate a constant maintenance infusion of 18 U/kg. Check the aPTT or Heparin Activity level 6 hours  Continue to check the aPTT  until 2 successive values are therapeutic.
Mangment  Heparin side effect heparin-induced thrombocytopenia (HIT).  elevation of serum aminotransferase levels Hyperkalemia alopecia and osteoporosis can occur with chronic use. Werfarin side effect Hemorrhage  Werfarin necrosis  Osteoporosis Purple toe syndrome
Filters for DVT indications for filter placement are  (1) severe hemorrhagic complications on anticoagulant therapy or other absolute contraindications to anticoagulation  (2) failure of anticoagulant therapy, such as new or recurrent venous thrombosis
Surgery for DVT  Indication anticoagulant therapy is ineffective Unsafe Contraindication The major surgical procedures for DVT are clot removal and partial interruption of the inferior vena cava to prevent PE
Treatment in pregnancy The treatment of DVT in pregnancy is similar to the treatment of non  pregnant. Heparin SC or small pump infusion  avoid warfarin in pregnancy If warfarin therapy is essential, it should be avoided at least during the first trimester (because of teratogenicity) and from about 2 to 4 weeks before delivery to reduce risk of hemorrhagic complications Compression stockings
Prevention Prophylaxis for DVT is required in all patients with risk factors. DVT prophylaxis for patients scheduled to undergo major surgery is well recognized.  Recently, a large multicenter double-blind placebo-controlled trial showed that a single subcutaneous 40-mg daily dose of enoxaparin achieved a 63% reduction in the incidence of DVT/PE in general medical patients admitted to the h ospital.
Prevention  In the Women's Health Study, supplementation with vitamin E (alpha-tocopherol, 600 IU every other day) reduced the risk of venous thrombo embolism in women, especially those with a prior history or genetic predisposition. High-risk patients should also be prescribed a single prophylactic subcutaneous 40 mg dose of enoxaparin prior to a long plane trip (>6 h).
Summary If deal with risk factor early can be prevent DVT Early detect & diagnosis prevent fetal complication DVT is 2 nd  cause of death in pregnancy wells  score& D-dimar and use of U/S can diagnosis DVT PE& post thrombatic syndrom most common complication
Reference  E medicine American family physicians Canadian family physicians Rakel essential family medicine Oxford handbook of clinical medicine Swansons family medicine review
 
workshop CALCULATE: Control events rate Experimental event rate RRR(Relative Risk Reduction) ARR (Absolute Risk Reduction) RR (Relative Risk) NNT(Number needed to treatment) Comments on the curves

DVT

  • 1.
    DVTDeep venous thrombosis) ) By Dr- Hayam M. AL-moutary Supervised by Dr-Abdulla AL-goblain
  • 2.
    Content Epidemiology Symptom& sign Risk factor Deferential diagnosis Diagnosis Management
  • 3.
    DVT the formationof a thrombus in the deep veins of the leg Virchow triad venous stasis vessel wall injury hypercoagulable state
  • 4.
    Epidemiology DVTsoccur in about 1 per 1000 persons per year. 100,000 deaths may be directly or indirectly related to these diseases In pregnant women, it has an incidence of 0.5 to 7 per 1,000 pregnancies, and is the second most common cause of maternal death in developed countries after bleeding Journal of Internal Medicine volume 232 Issue 2, Pages 155 - 160
  • 5.
    Risk factor General Age Immobilization longer than 3 days Pregnancy and the postpartum period Major surgery in previous 4 weeks Long plane or car trips (>4 h) in previous 4 weeks Medical Cancer Previous DVT Stroke Sepsis Nephrotic syndrome Ulcerative colitis SLE Protein c & s deficiency Obesity
  • 6.
    Risk factor Trauma Multiple trauma Drugs/medications OCP
  • 7.
    In a five-yearcase-control study (1988 to 1993) at Assir Central Hospital (ACH), Abha (8,000 feet above sea level), Saudi Arabia, 92 of 129 patients suspected of deep venous thrombosis (DVT) were studied with ascending contrast venography (CV) (74 patients, 80.4%) or Doppler ultrasonography (DUS) (18 patients, 19.6%). Female-to-male ratio was 2.3 to 1. Age range of patients was twelve to ninety years; mean age was 44.45 yrs ±17.38 years. DVT hospital incidence was 18 per 10,000 admissions Angiology, Vol. 46, No. 12, 1107-1113 (1995) http://ang.sagepub.com/cgi/content/abstract/46/12/1107
  • 8.
    Most risk factorchronic diseases (21.7%), trauma and surgery (19.6%), pregnancy and oral contraceptives usage (16.3%). most symptom and sig n tenderness (95.6%) Limb swelling was noted in 93.5% of patients. Pulmonary embolism was the greatest complication
  • 9.
    clinical feature swelling,principally unilateral, Leg pain occurs in 50% of patients SOB Clinical signs and symptoms of PE as the primary manifestation occur in 10% of patients with confirmed DVT In patients with angiographically proven PE, DVT is found in 45-70%.
  • 10.
    clinical feature Unilateraledema Leg tenderness Redness, hotness Bluish discoloration Absent or decrease pulse
  • 11.
    Clinical feature Phlegmasia cerulea dolens leg is cyanotic from massive ileofemoral venous obstruction. The leg is usually markedly edematous, painful, and cyanotic. Petechiae are often present . Phlegmasia alba dolens Painful white inflammation was originally used to describe massive ileofemoral venous thrombosis and associated arterial spasm. The affected extremity is often pale with poor or even absent distal pulses
  • 12.
  • 13.
    Clinical feature Superficial thrombophlebitis is characterized by the finding of a palpable, indurate, cordlike, tender, subcutaneous venous segment. 40% of patients with superficial thrombophlebitis without coexisting varicose veins and with no other obvious etiology (eg, intravenous catheters, intravenous drug abuse, soft tissue injury) have an associated DVT
  • 14.
  • 15.
    Deferential diagnosis Cellulitis,lymphangitis Lymphedema Postphlebitic syndrome Ruptured Baker cyst Varicose veins Superfical thrombophlibitis
  • 16.
    ( Diagnosis ( work up History Physical examination(work up) Probablity scoring (well score) Blood test D-dimar Other blood test Imaging study MRI , U/S , venography
  • 17.
    Physical examination Homans'test Dorsiflexion of foot elicits pain in posterior calf. Warning : it must be noted that it is of little diagnostic value and is theoretically dangerous because of the possibility of dislodgement of loose clot. Pratt's sign : Squeezing of posterior calf elicits pain. back
  • 18.
    Score (wells score) Clinical Parameter Score +1 Active cancer (treatment ongoing, or within 6 mo or palliative) +1 Paralysis or recent plaster immobilization of the lower extremities +1 Recently bedridden for >3 d or major surgery <4 wk +1 Localized tenderness along the distribution of the deep venous system +1 Calf swelling >3 cm compared with the asymptomatic leg +1 Pitting edema (greater in the symptomatic leg) +1 Previous DVT documented +1 Collateral superficial veins (nonvaricose) -2 Alternative diagnosis (as likely or greater than that of DVT)
  • 19.
    Wells score Total of Above Score > 3 High probability 1 or 2 Moderate probability < 0 Low probability
  • 20.
    case 35 yearold female recently pregnant, now on OCP, complain of 1 week unilateral right leg swelling , no history of trauma, she has DVT history 2year ago On P/E her right calf is 5 cm greater in circumference than her left and there is tenderness when squeeze the gastroncemius muscle.
  • 21.
    Blood test completeblood count Primary coagulation studies: PT, APTT, INR renal function test and electrolytes liver function test
  • 22.
    investigation D-dimer testing D-dimer antibodies account for their high sensitivity for venous thrombo embolism. D-dimer level may be elevated in any medical condition where clots form. D-dimer level is elevated in trauma, recent surgery, hemorrhage, cancer, and sepsis. The D-dimer assays have low specificity for DVT; therefore, they should only be used to rule out DVT, not to confirm the diagnosis of DVT .
  • 23.
    D-dimer results shouldbe used as follows : A negative D-dimer assay result rules out DVT in patients with low-to-moderate risk and a Wells DVT score less than 2. All patients with a positive D-dimer assay result and all patients with a moderate-to-high risk of DVT (Wells DVT score > 2) require a diagnostic study (duplex ultrasonography).
  • 24.
    Duplex ultrasonography Technologicaladvances in ultrasonography have permitted the combination of real-time ultrasonographic imaging with Doppler flow studies (duplex ultrasonography). The absence of the normal phasic Doppler signals arising from the changes to venous flow provides indirect evidence of venous occlusion
  • 25.
  • 26.
    Duplex ultrasonography Advantage helpful to differentiate venous thrombosis from hematoma, Baker cyst, abscess, and other causes of leg pain and edema. Disadvantage Venous thrombi proximal to the inguinal ligament are also difficult to visualize Nonoccluding thrombi not be able to differentiate between old and new clots
  • 27.
    MRI In thesecond and third trimester of pregnancy, MRI is more accurate than duplex ultrasonography because the gravid uterus alters Doppler venous flow characteristics. In suspected calf vein thrombosis, MRI is more sensitive than any other noninvasive study.
  • 28.
    MRI Disadvantage Expansive lack of general availability technical issues limit its use
  • 29.
    CT venography(gold stander)The gold standard is intravenous venography , which involves injecting a peripheral vein of the affected limb with a contrast agent and taking CT, to reveal whether the venous supply has been obstructed. Because of its invasiveness, this test is rarely performed
  • 30.
    CT venography(gold stander) A number of small studies have compared CT venography alone to duplex ultrasonography alone for the diagnosis of lower extremity DVT. Similar high sensitivities for ultrasonography and CT have been reported, but no large trials comparing the two have yet been performed
  • 31.
    CT venography(gold stander)Disadvantage visualized veins, artifactual interference from metal implants such as hip and knee arthroplasties . contraindications to the administration of contrast dye.
  • 32.
  • 33.
    High clinical pretestprobability- DVT likely Doppler ultrasound Ultrasound positive for DVT Diagnoses of DVT confirmed Begin treatment Ultrasound negative for DVT D-Dmer test (if available and reliable) Otherwise skip to repeat ultrasound D-Dimer positive Repeat ultrasound in 1 week D-Dimer negative DVT ruled out Repeat ultrasound positive for DVT Diagnoses of DVT confirmed Begin treatment Suspect DVT Low clinical pretest probability- DVT likely Consider starting with D-dimer test first (if available and reliable ) Or skip to ultrasound D-dimer positive D-Dimer negative DVT ruled out Doppler ultrasound Ultrasound positive for DVT Diagnose of DVT confirmed Begin treatment Ultrasound negative for DVT DVT ruled out (consider repeat ultrasound if D-dimer not available)
  • 34.
    Complications of deepvein thrombosis There are two main complications of deep vein thrombosis (DVT): pulmonary embolism post-thrombotic syndrome occurs in 15% of patients with deep vein thrombosis (DVT). It presents with leg oedema, pain, nocturnal cramping, venous claudication, skin pigmentation, dermatitis and ulceratiaion (usually on the medial aspect of the lower leg).
  • 35.
    management Non-pharmcological we can reduce risk of DVT by making changes to patient lifestyle, such as: avoid smoking eating a healthy balanced diet getting regular exercise and maintaining a healthy weight or losing weight if patient obese Rise leg , This reduces the pressure in the calf veins
  • 36.
    Travelling drink enoughamount of water avoid taking sleeping pills as it can cause immobility perform simple leg exercises, such as regularly flexing ankles take occasional short walks when possible wear elastic compression stockings
  • 37.
    Compression stockings Elastic compression stockings should be routinely applied &quot;beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis Most trials used knee-high stockings. A meta-analysis of randomized controlled trials by the Cochrane Collaboration showed reduced incidence of post-phlebitic syndrome.
  • 38.
    Treatment Thecurrent guidelines recommend short-term anticoagulation with LMWH SC , unfractionated heparin SC , (Grade 1A), should continue for at least 5 days and until the INR is > 2 for 24 hours (Grade 1C). Warfarin 5 mg PO daily is overlapped with heparin for 4-5 days until the international normalized ratio (INR) is therapeutically elevated to 2-3. For the first episode of DVT, patients should be treated for 3-6 months. Recurrent episodes should be treated for at least 1 year [Guideline] American Academy of Family Physicians
  • 39.
    Treatment Aprotocol for IV heparin use is as follows: Give an initial bolus of 80 U/kg Initiate a constant maintenance infusion of 18 U/kg. Check the aPTT or Heparin Activity level 6 hours Continue to check the aPTT until 2 successive values are therapeutic.
  • 40.
    Mangment Heparinside effect heparin-induced thrombocytopenia (HIT). elevation of serum aminotransferase levels Hyperkalemia alopecia and osteoporosis can occur with chronic use. Werfarin side effect Hemorrhage Werfarin necrosis Osteoporosis Purple toe syndrome
  • 41.
    Filters for DVTindications for filter placement are (1) severe hemorrhagic complications on anticoagulant therapy or other absolute contraindications to anticoagulation (2) failure of anticoagulant therapy, such as new or recurrent venous thrombosis
  • 42.
    Surgery for DVT Indication anticoagulant therapy is ineffective Unsafe Contraindication The major surgical procedures for DVT are clot removal and partial interruption of the inferior vena cava to prevent PE
  • 43.
    Treatment in pregnancyThe treatment of DVT in pregnancy is similar to the treatment of non pregnant. Heparin SC or small pump infusion avoid warfarin in pregnancy If warfarin therapy is essential, it should be avoided at least during the first trimester (because of teratogenicity) and from about 2 to 4 weeks before delivery to reduce risk of hemorrhagic complications Compression stockings
  • 44.
    Prevention Prophylaxis forDVT is required in all patients with risk factors. DVT prophylaxis for patients scheduled to undergo major surgery is well recognized. Recently, a large multicenter double-blind placebo-controlled trial showed that a single subcutaneous 40-mg daily dose of enoxaparin achieved a 63% reduction in the incidence of DVT/PE in general medical patients admitted to the h ospital.
  • 45.
    Prevention Inthe Women's Health Study, supplementation with vitamin E (alpha-tocopherol, 600 IU every other day) reduced the risk of venous thrombo embolism in women, especially those with a prior history or genetic predisposition. High-risk patients should also be prescribed a single prophylactic subcutaneous 40 mg dose of enoxaparin prior to a long plane trip (>6 h).
  • 46.
    Summary If dealwith risk factor early can be prevent DVT Early detect & diagnosis prevent fetal complication DVT is 2 nd cause of death in pregnancy wells score& D-dimar and use of U/S can diagnosis DVT PE& post thrombatic syndrom most common complication
  • 47.
    Reference Emedicine American family physicians Canadian family physicians Rakel essential family medicine Oxford handbook of clinical medicine Swansons family medicine review
  • 48.
  • 49.
    workshop CALCULATE: Controlevents rate Experimental event rate RRR(Relative Risk Reduction) ARR (Absolute Risk Reduction) RR (Relative Risk) NNT(Number needed to treatment) Comments on the curves

Editor's Notes

  • #41 heparin-induced thrombocytopenia (HIT). HIT is caused by an immunological reaction that makes platelets a target of immunological response, resulting in the degradation of platelets heparin-induced aldosterone suppression reduce bone mineral density
  • #46 vitamin E reduces the synthesis of thromboxane and increases the formation of prostacyclin. Thromboxane is considered the most potent platelet aggregating factor; therefore, further study on the role of vitamin E in regulating the metabolism of arachidonic