How Heparin Helps Prevent Recurrent Miscarriages - Verywell Family For individuals with antiphospholipid syndrome, the benefits of heparin usually outweigh the risks. Bruising happens, you get used to it. Therefore it is considered that heparin is safe for you to have whilst you are breastfeeding. there are no side effects except maybe I bruised slightly easier. In one study, women with recurrent pregnancy loss experienced a 71% subsequent live birth rate when treated with heparin and low-dose aspirin, compared to a 42% live birth rate for those given aspirin alone. How can I tell that my baby is getting enough milk? Mastery quiz questions Ch.12 Flashcards | Quizlet Now that is the way we do all of them! Cookies used to make website functionality more relevant to you. Read our, Lupus Anticoagulant Antibodies and Repeated Miscarriage, Causes of Miscarriage in the Second Trimester, Differences Between Miscarriage Risk Factors and Miscarriage Causes, Most Common Factors That Contribute to First Trimester Miscarriage, How a Septate Uterus Increases Miscarriage Risk, Thrombophilia and pregnancy complications, Aspirin plus heparin or aspirin alone in women with recurrent miscarriage, Polycystic ovary syndrome (an endocrine disorder in which the ovaries are enlarged and contain cysts), At least one confirmed instance of thrombosis, The loss of a fetus beyond 10 weeks of gestation, Placental insufficiency or preeclampsia that results in preterm delivery at 34 weeks or less, Three or more early miscarriages (within the first 10 weeks of pregnancy). Blood Clot in the Uterus During Pregnancy: Causes, Complications & Treatment, 170 Baby Boy & Girl Name That Mean 'Gift from God', 600+ Unique & Cute Nicknames for Boys & Girls, Protecting Adolescents From Common Food and Waterborne Diseases, Why an Ideal pH 5.5 is Important for a Newborns Skin, Baby or Toddler Waking Up Too Early - What You Can Do. 12/08/2006 at 2:58 pm. Warfarin is contraindicated during pregnancy, but is safe to use postpartum and is compatible with breastfeeding. This medication is given by injection into a vein or under the skin as directed by your doctor. Heparin Use in Pregnancy | Prisma Health Academics They postulated that unexplained miscarriages might be due to an unrecognized blood-clotting disorder. ]n^EkSfh-7wf9l^ifoio>ma_fq_n,B-/]KDw{hvS?n}"Ov$M t{o@M owG3| t>-K&A^}~Dzf&kA)R.D+-z vZ5__43Httiexies_yu}~6ui}+uzd[9u3Gq;w]l(PKdSn@"`j;Bg N 6kD`CLU(4ZZ`-H Studies reported only as abstracts were eligible for inclusion and would have been placed in studies awaiting assessment, pending the full publication of their results. All rights reserved. In addition, Stop the Clot, Spread the Word was one of many CDC resources recognized in 2017 as an important asset in a collection of VTE educational resources published by The Joint Commission. Lovenox (enoxaparin): Basics, Side Effects & Reviews - GoodRx Please feel free to share the campaigns educational resources with friends and family. Sometimes it may be diluted and given to you as a slow injection into one of your veins (this is called an intravenous infusion). Heparin is only recommended for use during pregnancy when benefit outweighs risk. Planning a Pregnancy or Expecting a Baby? Stop Lovenox or Dalteparin for 12 hours and begin unfractionated heparin at 10,000 u q 12 hours. Anticoagulation is sometimes needed during pregnancy and/or the postpartum period, including individuals at high risk of deep vein thrombosis, a history of venous thromboembolism, with prosthetic heart valves, atrial fibrillation, left ventricular dysfunction, or a history of fetal loss. It also induces Thrombocytopenia (low platelet count) in the mothers. ,VxB7fbFv`y`/_ Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. Verywell Family's content is for informational and educational purposes only. Consider the benefits and risks of heparin sodium for the mother and possible risks to the fetus when prescribing heparin sodium injection to a pregnant woman. If you need to go back and make any changes, you can always do so by going to our Privacy Policy page. Heparin is an anticoagulant, which prevents blood clotting. Clexane during pregnancy, birth and afterbirth | BabyCentre I was told today that I was going to have to Inject Clexane from now till 6 weeks after birth. Using heparin during pregnancy is not without risk. American College of Obstetricians and Gynecologists. Shelly- instead of emla or ametop which both take 45mins to an hour to work, you could use xzylocane Coldspray, which works instantly you just spray it on but its cold!!!! Breech baby at the end of Pregnancy and ECV, Pregnancy Related Pelvic Girdle Pain (PGP), Mendip Birth Centre - Southmead Hospital Bristol, Central Delivery Suite - Southmead Hospital Bristol, Spontaneous Rupture of the Membranes (SRM), Discharge Advice After an Epidural or Spinal Anaesthetic, Getting Breastfeeding off to a Good Start. :) I do heparin twice a day, on my morning injection I do the left side and in the evening I do the right side. Diagnosing DVT is difficult during pregnancy. And then administer the injection ask your Dr he could prescribe it. If eligible trials had been identified, trial quality would have been assessed and data extracted, unblinded by review authors independently. They help us to know which pages are the most and least popular and see how visitors move around the site. she suggested that I give my shots directly instead of at an angle which has really made a difference. Clexane during pregnancy, birth and afterbirth. x\_s=x8iu'I}pRN&_ v7/yY4g/d#e+Ll'o3[e]L4{)W>FhK?_.v3[IOg.tc:9L} Zp#%E^^GvMrTlf3y>>6qaf8t|E6J Should you have any concerns about your health, or of that of your baby or child, please consult with We take your privacy seriously. Right now I have a HUGE cruise on my right side because I scratched my tummy on a chair so I've been injecting just on the left side for about 2 weeks and I've been fine. Quasi-randomised studies and cross-over trials were not eligible for inclusion.. Methods of administering subcutaneous heparin include intermittent injections versus indwelling catheters or programmable (auto) external infusion pumps, or any other devices to facilitate the subcutaneous administration of heparin (UFH or LMWH) during pregnancy. Begin unfractionated heparin at 333 u/kg subcutaneous and then 250 u/kg subcutaneous q 12 hours. I hardly bruise at all. Pregnancy, Blood Clots and Anticoagulation Lovenox (enoxaparin) is an anticoagulant (blood thinner) that works by blocking the activity of certain blood-clotting proteins. How to Give an Anticoagulant (Blood Thinner) Shot: Care - Alberta 2.2 Women may use opioids as prescribed, may misuse prescription opioids, may use illicit opioids such as heroin, or may use opioids as part of medication-assisted treatment for opioid use disorder. There are various types of heparin the type we usually use is a Low Molecular Weight Heparin (LMWH) such as Enoxaparin (also known as Clexane) or Dalteparin. It is important that the heparin is given at the same time of day (within two hours) and it is recommended that it be given in the morning if the blood tests to monitor it are needed. The experience of one miscarriage is devastating, let alone recurrent miscarriages. <> Factor V Leiden and prothrombin G20210A mutation are the most common inherited thrombophilias, and antiphospholipid antibody syndrome is the most important acquired defect. Pulmonary embolism typically presents postpartum with dyspnea and tachypnea. interactive elements on the site, any assistance, or response you receive is provided by the author Laurali Addison edd 6/26/09; tenative induction 6/23/09, I just learned that after numerous miscarriages that I will be starting heparin injections once I have a negative pregnancy test. Thrombophilia disorders are also thought to cause other issues with the placenta., Bloodwork helps identify certain markers to diagnose antiphospholipid syndrome. She has written articles on pregnancy, parenting, and relationships. Are the heparin injections more painful than the progesterone? This means that is slows down blood clotting or "thins" the blood. There were no problems throughout the pregnancy. Some people prefer to inject the heparin fast, but I prefer to go slowly. Administer Heparin Sodium Injection by intermittent intravenous injection, intravenous infusion, or deep subcutaneous (intrafat, i.e., above the iliac crest or abdominal fat layer) injection. Just curious as I am concerned I will develop more hard lumps. When all the heparin has been injected, slowly withdraw the needle at the same angle at which it entered, releasing the skin roll as you withdraw. I lie down and then just squeeze an inch of skin/fat and inject at a 45 degree angle. If available, preservative-free heparin sodium injection is recommended when heparin therapy is needed during pregnancy. Is this normal? UpToDate Side effects of heparin treatment may include bleeding and decreased bone density. Do not rub the area. Pregnant women with a history of VTE, antithrombin deficiency, or other risk factors for VTE are at an even greater risk and need heparin for prevention of VTE (prophylaxis). Also, you want to stay at least 2 inches AWAY from your belly button to avoid the higher concentration of veinswhich can lead to bruising and swelling. Suitable injection sites include the sides of your tummy (avoiding the area near Unfortunately, a 2010 study found that neither heparin nor low-dose aspirin improved birth rates in patients without antiphospholipid antibodies. Do not pre-press on the piston protrusion to remove air bubbles, as this may disturb the dosage of the drug. The upper outer side of the thigh. The best places for you to inject into are: The U-shape area around your belly button. CDC and NBCA have launched new content for their digital public health education campaign called Stop the Clot, Spread the Word. Heparin is also used to treat blood clots when they do form, helping prevent the clot from . DailyMed - HEPARIN SODIUM injection Methods of receiving heparin subcutaneously include giving an injection at regular intervals, or using an indwelling catheter and an infusion pump. Make sure you're rotating spots so to not make one area more sore than other spots. endobj Expecting or recently had a baby? Using heparin during pregnancy is not without risk. Hello! 2.1 Preparation for Administration. The #1 app for tracking pregnancy and baby growth. LMWHs are the agents of choice for antenatal thromboprophylaxis. I wouldn't inject where the bruise is cause that would probably hurt pretty bad. fsikrfJ/WK%HBKhT-XY Whether women are treated with heparin, or LMWH, they will ultimately need to receive once or twice-daily injections until at least 6 weeks after delivery of the baby. Mumsnet carries some affiliate marketing links, so if you buy something through our posts, we may get a small share of the sale (more details here). [PDF 3.24 MB]The Commission accredits and certifies nearly 21,000 healthcare organizations in the United States. Using epoetin alfa injection products increases the risk that blood clots will form in or move to the legs, lungs, or brain. The discovery of LMWH has indeed been a boon to many mothers suffering from blood clotting problems as blood clotting does pose a major threat during the period of pregnancy. (I was diagnosed with a Sub-clavian Vein thrombosis 2008, Thrombophillya test boarder line) I was not told then that it would affect any future pregnancies so this . About Opioid Use During Pregnancy | CDC Preparing Heparin Download Article 1 Wash your hands. As long as its not overly painful it should be ok. You may want to ask about it at your next dr appt if it makes you feel better. Expecting or Recently had a Baby? Heparin Injection: MedlinePlus Drug Information Warfarin, another anticoagulant taken in tablet form, does cross the placenta and may harm the unborn child (tetrogenic). I just switched to heparin (2x/day) and I do one side at night, the other in the morning. The nurse that taught both myself and my husband to inject myself had that happen to her. Is It Safe to Use Heparin During Pregnancy? DailyMed - HEPARIN SODIUM injection Good luck and congrats!!!! Venous compression (Doppler) ultrasonography is the diagnostic test of choice. Good luck! Women who are aware of their blood clotting problems are recommended to check with their doctors first and start the medication as prescribed. 7 Clinical presentation varies from mild dyspnea and tachypnea to dramatic cardiopulmonary collapse. You will be shown how to give yourself the injections before you go home but this leaflet also gives you instructions. Study with Quizlet and memorize flashcards containing terms like While being on subcutaneous heparin injections for deep vein thrombosis during her latter pregnancy, a patient begins to experience major side effects. You really want to make sure you aren't injecting in the same area. A DVT can limit blood flow through the vein, causing swelling and pain, but there is a risk that it can break off and travel through the blood stream. While everyone is at risk for developing a blood clot (also called venous thromboembolism or VTE), pregnancy increases that risk fivefold. What Is Heparin and Why Is It Recommended During Pregnancy? Do not rub. <>/XObject<>/Pattern<>/ProcSet[/PDF/Text/ImageB/ImageC/ImageI] >>/MediaBox[ 0 0 595.32 841.92] /Contents 4 0 R/Group<>/Tabs/S/StructParents 0>> There is another kind of heparin, which has been recently recommended by doctors to pregnant women and in general to stop blood clots. Safe Sleeping & Caring for your Baby at Night, Southwest Neonatal Network Donor Milk Bank. There is also another thread with tips. All rights reserved. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Heparin Injection During Pregnancy - youdrugstore.com I don't really have alot more to add than the previous posters but, I have beenon heaprin now for almost 5 wks and at first i was bruising very badly and was using my inner thighs (while sitting down) as my injection sites. Epoetin Alfa, Injection: MedlinePlus Drug Information Heparin is also used to treat venous thrombosis, but the dose of heparin used to prevent a venous thrombosis is 3 0 obj "DOC'$), $V@,0 =M-`>[ EPM`JL ,VJO !Js2=@oy. Don't inject in that spot again til the bruising is gone. Every story is different, but below . Results - Information about being a carrier. Labor & Delivery on Blood Thinner | My Heparin & Lovenox Pregnancy Thromboprophylaxis during pregnancy By subcutaneous injection Adult 5000-10 000 units every 12 hours, to be administered with monitoring, Important: prevention of prosthetic heart-valve thrombosis in pregnancy calls for specialist management. It is important that you change the site each time. Sasaki H, Yonemoto N, Hanada N, Mori R. Methods for administering subcutaneous heparin during pregnancy. Hi there- I have been on lovenox and heparin for this pregnancy( ANA+) and I have found that warming the meds up for a few minutes makes it sting MUCH less. Let it dry. IJMS. That is wonderful information and answers a lot of questions!! Signs and symptoms of a PE include, Chest pain that worsens with a deep breath or cough, Faster than normal or irregular heartbeat. Warfarin is NOT to be taken when pregnant because it will effect the baby so Lovenox / heparin shots are often prescribed seeing as it is faster acting . After deep subcutaneous (intrafat) injections, tests for adequacy of dosage are best performed on samples drawn 4 to 6 hours after the injection. Recent findings: Low-molecular-weight heparins do not increase the risk of maternal bleeding during pregnancy. It is considered safe since it does not penetrate the placenta. All Rights Reserved. Pregnant? The welcome thread at the top of page one has lots of tips in it. Cochrane Database of Systematic Reviews 2013, Issue 3. Symptoms of dyspnea are nonspecific in pregnancy. LMWHs are recommended for the treatment of acute DVT and PE in pregnancy because of equivalent or superior effectiveness and safety compared with unfractionated heparin. It is safe to inject LMWH into the abdomen while pregnant. Wash your hands before giving the injection. It's best to use one of the following areas (see Figure 1): Your abdomen (belly), except for the 2-inch (5-centimeter) area around your belly button The middle front or middle outside of your thighs 'sAc6 fm/1Gdyzc%ott @TwinkleStars15 that's really awesome to hear! I started out numbing with ice but that just took too long lol. Haemodialysis Initially by intravenous injection Adult Venous thrombosis is a condition in which a blood clot (thrombus) forms in a vein (venous thrombosis). Heparin Use During Pregnancy | North Bristol NHS Trust - NBT Low-dose aspirin and low-molecular-weight heparin (LMWH . I haven't done anything differently that I'm aware of. Her OB physician has called in a specialist who thinks the patient is experiencing heparin-induced thrombocytopenia. Copyright 2023 American Academy of Family Physicians. Vaccination During Pregnancy: Which Vaccines Do You Need? - Parents I really feel like they haven't been wonderful about communicating with me about any of this. It must be given by injection into the fatty layer of tissue beneath the skins. Use heparin sodium during pregnancy only if the potential benefit justifies the potential risk to the fetus. Should I have it checked? Warfarin is contraindicated during pregnancy, but is safe to use postpartum and is compatible with breastfeeding. Best of luck! Heparin injections "thin" the blood, decreasing the tendency to form clots. If you could give me some advice/tips, I would REALLY appreciate it!! KING, MD, MPH. Continuous IV infusion for a total of at least 30,000 IU over 24 hours, Monitor aPTT and adjust dose to maintain aPTT 1.5 to 2 times control value, DVT or PE with thrombogenic event (e.g., hip fracture, prolonged surgery), Antithrombin deficiency, homozygous factor V Leiden; two or more minor risk factors (i.e., heterozygous factor V Leiden and heterozygous prothrombin G20210A mutations), Single heterozygous factor V Leiden or heterozygous prothrombin G20210A mutation. <>/PageLabels 375 0 R>> Treat the intended injection with a cotton pad moistened with alcohol. Although, the low molecular weight heparin is considered safe to use with regards to pregnancy, the Unfractionated Heparin version used before had several health risks associated with it. AND, it's hard. Be sure to talk with your healthcare provider to understand the best course of management for you. N Engl J Med. Our website is not intended to be a substitute for professional medical advice, diagnosis, or treatment. . Staying hydrated during pregnancy helps prevent clots by keeping the blood from getting too thick, Roshan said. %PDF-1.5 Check APTT or antifactor Xa level once in 7 days. 1. Blood Clot Prevention Checklist for Pregnant Women, Blood Clot Risk Checklist for Pregnant Women, This Is Serious (Duke Haemostasis Center), Join the Public Health Webinar Series on Blood Disorders. Monitoring for these is part of your clinic visit, but the more serious side effects are almost never seen with LMWH use in pregnancy. Download these checklists to learn more about your risks for blood clots and how to guide a discussion with your healthcare provider. The National Blood Clot Alliance (NBCA), a leading VTE advocacy group in North America, was funded through a five-year cooperative agreement to help address the lack of education on blood clots for the public. Some women might already be taking the injections, and some might begin during their term of pregnancy. l= x FwdjEM!uULSQx44DVT The only slight difficulty was that you can't have an epidural within 24 hours of your last heparin injection. The effect of unfractionated heparin in assisted reproductive technology (ART) cycles is prevention of thrombosis in implantation site . Clinical symptoms of deep venous thrombosis may be subtle and difficult to distinguish from gestational edema. It is used to treat and prevent deep vein thrombosis (DVT) and pulmonary embolism (PE) including during pregnancy and following certain types of surgery. How to inject Heparin subcutaneously | RIA Labs A PE may cause breathing problems, chest pain and coughing up blood but a large PE can cause collapse and may be life threatening. I know I asked my dr about the bumps in the beginning and she said it was perfectly normal. (I tried it). Grasp the tip of the Needle-Trap and bend it away from the syringe. Low-Dose Low-Molecular-Weight Heparin for Thromboprophylaxis During Heparin, medically known as Unfractionated Heparin (UFH), is an anticoagulant which is used to stop blood clotting. This is called an embolus. UpToDate, electronic clinical resource tool for physicians and patients that provides information on Adult Primary Care and Internal Medicine, Allergy and Immunology, Cardiovascular Medicine, Emergency Medicine, Endocrinology and Diabetes, Family Medicine, Gastroenterology and Hepatology, Hematology, Infectious Diseases, Nephrology and Hypertension, Neurology, Obstetrics, Gynecology, and Women . Heparin and LMWH have been used in pregnancy by thousands of women with no birth defects or bleeding problems in their unborn babies. Heparin injections in pregnancy | Mumsnet Unfortunately, not knowing the cause of miscarriage makes it difficult to know what to expect if you choose to become pregnant again. Table 1 lists a typical therapeutic LMWH dose.10,12,32,41 The optimal monitoring protocol with LMWH is controversial. % The specific form of thrombophilia that's most often tied to miscarriage is calledantiphospholipid syndrome. Guide to Anticoagulant Therapy: Heparin | Circulation Use of Anticoagulants during Pregnancy - CHEST I have been on heparin shots for a bit now. Dont let a blood clot spoil your joy. Heparin During Pregnancy and Breastfeeding | babyMed.com 2 Remove the cap and roll the vial. If it starts to burn, I go slowersometimes I pull the needle out just a teensy bit and proceed to inject the heparin. I make sure to avoid veins, even if it takes me a few extra seconds I make sure I am in a good light and look to avoid them. Women who take warfarin must switch to heparin or low molecular weight heparin before they become pregnant, since heparin or low molecular weight heparin (Lovenox, Fragmin) do not cross the placenta into the fetus. Confirm the choice of the correct HEPARIN SODIUM INJECTION vial to ensure that the 1 mL vial is not confused with a "catheter lock flush" vial or other 1 mL vial of incorrect strength [se e Warnings and Precautions (5.1)]. It does not cross the placenta, and therefore is considered to be safe. However, the use of other blood thinners such as Warfarin and Unfractionated Heparin (the type that was previously used) may pose a threat to the health of the mother as well as the baby. This is called a pulmonary embolism (PE), and can be life threatening. A management plan for the heparin will be made which should be kept in your obstetric notes and a copy will be kept in your medical notes. Some of the most common heparin side effects during pregnancy include: Heparin injection during pregnancy is usually administered to control blood clotting. endobj Other diagnostic criteria for the syndrome include:. Heparin injection - Netdoctor He is the director and founding partner of CCRM New York and was named a rising star by Super Doctors from 2017 to 2019. By clicking Accept All Cookies, you agree to the storing of cookies on your device to enhance site navigation, analyze site usage, and assist in our marketing efforts. Generic Enoxaparin Questions and Answers | FDA Heparin Sodium Market - Covid-19 Impact and Recovery Analysis: We have been tracking the direct impact of COVID-19 on this market, as well as the indirect impact from other industries. Heparin Injection (Heparin sodium) Drug / Medicine Information The form of heparin that's preferred during pregnancy is called low molecular weight heparin (LMWH). Heparin During Pregnancy - Is It Safe to Use? - FirstCry Parenting Methods of receiving heparin subcutaneously include giving an injection at regular intervals, or using an indwelling catheter and an infusion pump. Heparin is an anticoagulant drug. It is not known whether heparin is excreted into breast milk. Heparin is also known as: Heparin Sodium Pregnancy Warnings Breastfeeding Warnings Heparin Pregnancy Warnings Animal studies have revealed increased resorptions at doses approximately 10 times higher than the maximum human daily dose based on body weight. Push down on the plunger slowly as far as it will go. General Precautions: Heparin is considered safe for use during pregnancy, mostly because it does not cross the placenta and thus does not reach the baby. However, they are harmful because they are associated with an increased risk of thromboembolic, hemorrhagic, or microcirculatory disturbances or placental dysfunction leading to fetal growth restriction or loss. Heparin does not cross the placenta, and thus, it was surprising that a recent report concluded that heparin therapy during pregnancy was as risky as oral anticoagulant therapy. A PE may cause breathing problems, chest pain and coughing up blood but a large PE can cause collapse and may be life threatening. The use of low-molecular-weight heparins in pregnancy--how safe are Your doctor can discuss the costs and benefits of taking heparin to help you understand what side effects to look out for and decide whether it's right for you. Experts have theorized that heparin may prevent recurrent miscarriages even in patients who test negative for antiphospholipid antibodies. Your risk of developing a thrombosis will be assessed in pregnancy and after the birth of your baby. The investigation found that a heparin regimen, which is administered by injection, did not reduce the incidence of serious blood clots, miscarriage or stillbirth among women deemed to be at. I also am really scared about how painful this will be. Lovenox is perfectly safe. Based on data from nonpregnant patients, PE can be excluded with a normal or low probability V/Q scan if clinical suspicion is low to moderate.25 Likewise, PE can be diagnosed with a high probability scan if clinical suspicion is moderate to high.25 In a study of V/Q scanning in 120 pregnant women with suspected PE, 73.5 percent were normal and 1.8 percent were high probability, compared with 27 to 36 percent normal and 8 to 14 percent high probability scans in nonpregnant patients.31 When V/Q scanning is nondiagnostic, additional options include repeat leg compression ultra-sonography, repeat V/Q scanning, spiral computed tomography, magnetic resonance imaging, and pulmonary angiography. VTE includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Heparin should not be injected into a muscle. Compared to other variants, LMWH is better absorbed, lasts longer, and isn't associated with as much bone loss., Studies on heparin for patients with known antiphospholipid syndrome are encouraging. It crosses the placenta and increases the risk of miscarriage, stillbirth, embryopathy (nasal hypoplasia or stippled epiphyses), central nervous system abnormalities, and maternal and fetal hemorrhage.32 Warfarin is compatible with breastfeeding.32, Data derived from nonpregnant populations suggest that therapeutic anticoagulation following a first episode of VTE should continue for at least six months from diagnosis.38 Current recommendations for the duration of treatment in pregnancy range from three to six months, including six weeks postpartum.10,12,32 Long-term (i.e., longer than 12 months) anticoagulation is indicated for women with VTE and antiphospholipid antibody syndrome, or two or more thrombophilias,39 and for women with any thrombophilia and recurrent thrombotic events.40.
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