Anticoagulation in pregnancy
Encyclopedia
Hypercoagulability in pregnancy is the propensity of pregnant women to develop thrombosis
(blood clots). Pregnancy itself is a factor of hypercoagulability (pregnancy-induced hypercoagulability) as a physiologically adaptive mechanism to prevent postpartum hemorrhage
. However, when combined with an additional underlying hypercoagulable states, the risk of thrombosis or embolism may become substantial.
. Pregnancy changes the plasma levels of many clotting factors like fibrinogen
, which can rise up to three times the normal value. Thrombin
levels increase. Protein S
, an anticoagulant, decreases. However, the other major anticoagulants, protein C
and antithrombin III, remain constant. Fibrinolysis
is impaired by an increase in plasminogen activator inhibitor-1
(PAI-1 or just PAI) and plasminogen activator inhibitor-2
(PAI-2), the latter synthesized from the placenta. Venous stasis
may occur at the end of the first trimester, due to enhanced compliance of the vessel walls by a hormonal effect.
There are also many pregnancy-related causes of hypercoagulability, e.g. the prolonged bed rest that often occurs postpartum that occurs in case of delivery by forceps
, vacuum extractor or Caesarean section
. Pregnancy after the age of 35 augments the risk of VTE, as does multigravidity of more than 4 pregnancies. Several pregnancy complications
, like preeclampsia, cause substantial hypercoagulability.
General causes of hypercoagulability, that are approximately as common in pregnancy as in the general population, include both acquired ones such as antiphospholipid antibodies, and congenital ones, including Factor V Leiden mutation, prothrombin mutation, protein C
and S
deficiencies and antithrombin III deficiency
.
has an incidence of 1 in 1,000 to 2,000 pregnancies in the United States, and is the second most common cause of maternal death
in developed countries after bleeding.
, changes in the anticoagulation regimen during pregnancy can be performed to minimize the risks to the developing fetus while maintaining therapeutic levels of anticoagulation in the mother.
The main issue with anticoagulation in pregnancy is that warfarin
, the most commonly used anticoagulant in chronic administration, is known to have teratogenic effects
on the fetus if administered in early pregnancy. Still, there seems to be no teratogenic effect of warfarin before 6 weeks of gestation. On the other hand, unfractionated heparin
and low molecular weight heparin
(LMWH) do not cross the placenta.
, a metallic prosthetic heart valve
, and atrial fibrillation
in the setting of structural heart disease.
In addition to these indications, anticoagulation may be of benefit in individuals with SLE
and a history of previous spontaneous abortions, individuals who have a history of deep venous thrombosis (DVT) or pulmonary embolism
(PE) associated with a previous pregnancy, and even with individuals with a history of coagulation factor deficiencies and DVT not associated with a previous pregnancy.
inhibiting agents are contraindicated during the first trimester of pregnancy because of the teratogenic effects, and should not be administered when pregnancy confirmed. Rather, women who are on chronic anticoagulation may be given the option of conversion to either unfractionated heparin
or low molecular weight heparin
(LMWH) such as tinzaparin
prior to a planned conception
. LMWH is as safe and efficacious as unfractionated heparin. A blood test
including platelets and a clotting screen should be performed prior to administration of anticoagulant regimens in pregnancy.
Subcutaneous tinzaparin may be given at doses of 175 units of anti-factor Xa activity per kg, based on pre-pregnancy or booking weight at approximately 16 weeks, and not the current weight. While unfractionated heparin is otherwise typically given in an intravenous formulation, this is inconvenient for the prolonged period of administration required in pregnancy.
Whether warfarin can be re-initiated after the twelfth week of pregnancy is unclear. In a recent retrospective analysis, it was suggested that resumption of warfarin after the first trimester is completed is associated with increased risk of loss of the fetus. However, this analysis included only individuals who were anticoagulated for mechanical heart valves, which generally require high levels of anticoagulation.
In pregnant women with mechanical heart valves, the optimal anticoagulation regimen is particularly unclear. It is clear from prior studies that anticoagulation with subcutaneous heparin in this setting is associated with a high incidence of thrombosis
of the valve and death. Similar issues are likely associated with the use of enoxaparin
(a low molecular weight heparin
) in these high-risk individuals.
After adding any risk factors together, a total of 1 point or less indicates that no preventive action is needed. A total of 2 points indicates that short-term prophylaxis, e.g. with low molecular weight heparin
, may be used in temporary risk factors, as well as administering prophylactic treatment 7 days postpartum, starting a couple of hours after birth. A total of 3 points increases the necessary duration of postpartum prophylaxis to 6 weeks.
A risk score of 4 points or higher means that there should probably be prophylaxis in the antepartum period, as well as at least 6 weeks postpartum. A previous distal DVT motivates a minimum of 12 weeks (3 months) of therapeutic anticoagulation therapy A previous proximal DVT or pulmonary embolism motivates a minimum of 26 weeks (6.5 months) of therapy If the therapy duration reaches delivery time, the remaining duration may be given postpartum, possibly extending the minimum of 6 weeks postpartum therapy. In a very high risk, there should be a high-dose antepartum prophylaxis, continued at least 12 weeks postpartum.
Women with antiphospholipid syndrome
should have an additional low dose prophylactic treatment of Aspirin
.
, thrombocytopaenia, liver disease
and nephropathy
.
Major side effects of tinzaparin
are osteoporosis
(occurring in up to 1% of cases), thrombocytopenia
(heparin-induced thrombocytopenia
), haemorrhage, hair loss and drug allergy
. Still, LMWHs are much less likely to cause heparin-induced thrombocytopenia than unfractionated heparin.
Regional anaesthesia
is contraindicated in women on therapeutic anticoagulation, and should not be used within 24 hours of the last dose of tinzaparin.
(PT) or the INR, and Anti Xa levels are not reliable. It can prolong the Partial thromboplastin time
(APTT) in some women, but still, the APTT is not useful for monitoring.
In order to check for any thrombocytopenia, platelet count should be checked prior to commencing anticoagulant therapy, then 7 to 10 days after commencement, and monthly thereafter. Platelet count should also be checked if unexpected bruising or bleeding occurs.
reverses the effect of unfractionated heparin but only partially binds to and reverses LMWH. A dose of 1mg protamine/100IU LMWH reverses 90% of its anti-IIa and 60% of anti-Xa activity, but the clinical effect of the residual anti Xa activity is not known. Both anti-IIa and anti
Xa activity may return up to three hours after protamine reversal, possibly due to release of additional LMWH from depot tissues.
.
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
(blood clots). Pregnancy itself is a factor of hypercoagulability (pregnancy-induced hypercoagulability) as a physiologically adaptive mechanism to prevent postpartum hemorrhage
Postpartum hemorrhage
Hemorrhage after delivery, or postpartum hemorrhage, is the loss of greater than 500 ml of blood following vaginal delivery, or 1000 ml of blood following cesarean section...
. However, when combined with an additional underlying hypercoagulable states, the risk of thrombosis or embolism may become substantial.
Causes
Pregnancy-induced hypercoagulability is probably a physiologically adaptive mechanism to prevent postpartum hemorrhagePostpartum hemorrhage
Hemorrhage after delivery, or postpartum hemorrhage, is the loss of greater than 500 ml of blood following vaginal delivery, or 1000 ml of blood following cesarean section...
. Pregnancy changes the plasma levels of many clotting factors like fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
, which can rise up to three times the normal value. Thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
levels increase. Protein S
Protein S
Protein S is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b. In humans, protein S is encoded by the PROS1 gene...
, an anticoagulant, decreases. However, the other major anticoagulants, protein C
Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals...
and antithrombin III, remain constant. Fibrinolysis
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
is impaired by an increase in plasminogen activator inhibitor-1
Plasminogen activator inhibitor-1
Plasminogen activator inhibitor-1 also known as endothelial plasminogen activator inhibitor or serpin E1 is a protein that in humans is encoded by the SERPINE1 gene....
(PAI-1 or just PAI) and plasminogen activator inhibitor-2
Plasminogen activator inhibitor-2
Plasminogen activator inhibitor-2 is a coagulation factor that inactivates tPA and urokinase. It is present in most cells, especially monocytes/macrophages...
(PAI-2), the latter synthesized from the placenta. Venous stasis
Venous stasis
Venous stasis, or venostasis, is a condition of slow blood flow in the veins, usually of the legs. A patient with venous stasis might be more vulnerable to the formation of blood clot, especially in the deep veins of the legs, called deep vein thrombosis .Causes include long periods of immobility...
may occur at the end of the first trimester, due to enhanced compliance of the vessel walls by a hormonal effect.
There are also many pregnancy-related causes of hypercoagulability, e.g. the prolonged bed rest that often occurs postpartum that occurs in case of delivery by forceps
Forceps in childbirth
Forceps are a surgical instrument that resembles a pair of tongs and can be used in surgery for grabbing, maneuvering, or removing various things within or from the body...
, vacuum extractor or Caesarean section
Caesarean section
A Caesarean section, is a surgical procedure in which one or more incisions are made through a mother's abdomen and uterus to deliver one or more babies, or, rarely, to remove a dead fetus...
. Pregnancy after the age of 35 augments the risk of VTE, as does multigravidity of more than 4 pregnancies. Several pregnancy complications
Complications of pregnancy
Complications of pregnancy are the symptoms and problems that are associated with pregnancy. There are both routine problems and serious, even potentially fatal problems. The routine problems are normal complications, and pose no significant danger to either the woman or the fetus...
, like preeclampsia, cause substantial hypercoagulability.
General causes of hypercoagulability, that are approximately as common in pregnancy as in the general population, include both acquired ones such as antiphospholipid antibodies, and congenital ones, including Factor V Leiden mutation, prothrombin mutation, protein C
Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals...
and S
Protein S
Protein S is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b. In humans, protein S is encoded by the PROS1 gene...
deficiencies and antithrombin III deficiency
Antithrombin III deficiency
Antithrombin III deficiency is a rare hereditary disorder that generally comes to light when a patient suffers recurrent venous thrombosis and pulmonary embolism...
.
Complications
Deep vein thrombosisDeep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...
has an incidence of 1 in 1,000 to 2,000 pregnancies in the United States, and is the second most common cause of maternal death
Maternal death
Maternal death, or maternal mortality, also "obstetrical death" is the death of a woman during or shortly after a pregnancy. In 2010, researchers from the University of Washington and the University of Queensland in Brisbane, Australia, estimated global maternal mortality in 2008 at 342,900 , of...
in developed countries after bleeding.
Prevention of thrombosis with anticoagulants
While the consensus among physicians is that the safety of the mother supersedes the safety of the developing fetusFetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
, changes in the anticoagulation regimen during pregnancy can be performed to minimize the risks to the developing fetus while maintaining therapeutic levels of anticoagulation in the mother.
The main issue with anticoagulation in pregnancy is that warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
, the most commonly used anticoagulant in chronic administration, is known to have teratogenic effects
Teratology
Teratology is the study of abnormalities of physiological development. It is often thought of as the study of human birth defects, but it is much broader than that, taking in other non-birth developmental stages, including puberty; and other non-human life forms, including plants.- Etymology :The...
on the fetus if administered in early pregnancy. Still, there seems to be no teratogenic effect of warfarin before 6 weeks of gestation. On the other hand, unfractionated heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
and low molecular weight heparin
Low molecular weight heparin
In medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
(LMWH) do not cross the placenta.
Indications
In general, the indications for anticoagulation during pregnancy are the same as the general population. This includes (but is not limited to) a recent history of deep venous thrombosis (DVT) or pulmonary embolismPulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
, a metallic prosthetic heart valve
Artificial heart valve
An artificial heart valve is a device implanted in the heart of a patient with heart valvular disease. When one of the four heart valves malfunctions, the medical choice may be to replace the natural valve with an artificial valve. This requires open-heart surgery.Valves are integral to the normal...
, and atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
in the setting of structural heart disease.
In addition to these indications, anticoagulation may be of benefit in individuals with SLE
Lupus erythematosus
Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
and a history of previous spontaneous abortions, individuals who have a history of deep venous thrombosis (DVT) or pulmonary embolism
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
(PE) associated with a previous pregnancy, and even with individuals with a history of coagulation factor deficiencies and DVT not associated with a previous pregnancy.
Strategies
There is no consensus on the correct anticoagulation regimen during pregnancy. Treatment is tailored to the particular individual based on their risk of complications. Warfarin and other vitamin KVitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
inhibiting agents are contraindicated during the first trimester of pregnancy because of the teratogenic effects, and should not be administered when pregnancy confirmed. Rather, women who are on chronic anticoagulation may be given the option of conversion to either unfractionated heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
or low molecular weight heparin
Low molecular weight heparin
In medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
(LMWH) such as tinzaparin
Tinzaparin
Tinzaparin is an antithrombotic drug in the heparin group. It is a low molecular weight heparin marketed as Innohep worldwide. It has been approved by the U.S. Food and Drug Administration for once daily treatment and prophylaxis of deep vein thrombosis and pulmonary embolism...
prior to a planned conception
Fertilisation
Fertilisation is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo...
. LMWH is as safe and efficacious as unfractionated heparin. A blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
including platelets and a clotting screen should be performed prior to administration of anticoagulant regimens in pregnancy.
Subcutaneous tinzaparin may be given at doses of 175 units of anti-factor Xa activity per kg, based on pre-pregnancy or booking weight at approximately 16 weeks, and not the current weight. While unfractionated heparin is otherwise typically given in an intravenous formulation, this is inconvenient for the prolonged period of administration required in pregnancy.
Whether warfarin can be re-initiated after the twelfth week of pregnancy is unclear. In a recent retrospective analysis, it was suggested that resumption of warfarin after the first trimester is completed is associated with increased risk of loss of the fetus. However, this analysis included only individuals who were anticoagulated for mechanical heart valves, which generally require high levels of anticoagulation.
In pregnant women with mechanical heart valves, the optimal anticoagulation regimen is particularly unclear. It is clear from prior studies that anticoagulation with subcutaneous heparin in this setting is associated with a high incidence of thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
of the valve and death. Similar issues are likely associated with the use of enoxaparin
Enoxaparin
Enoxaparin is a low molecular weight heparin marketed under the trade names Lovenox and Clexane, among others. It is an anticoagulant used to prevent and treat deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection...
(a low molecular weight heparin
Low molecular weight heparin
In medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
) in these high-risk individuals.
By risk score
Prevention of deep vein thrombosis and other types of venous thrombosis may be required if there are certain predisposing risk factors. One example is based on the point system below, where points are summed together to give the appropriate prophylaxis regimen.| Points | Risk factors |
|---|---|
| 1 point Minor factors |
|
| 2 points Intermediate risk factors |
Protein S Protein S is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b. In humans, protein S is encoded by the PROS1 gene... or C Protein C Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals... deficiency Bone fracture A bone fracture is a medical condition in which there is a break in the continuity of the bone... or prolonged bed rest Bed rest Bed rest is a medical treatment involving a period of consistent recumbence in bed. It is used as a treatment for an illness or medical condition, especially when prescribed or chosen rather than resulting from severe prostration or imminent death... |
| 3 points Intermediate risk factors |
Factor V Leiden Factor V Leiden is the name given to a variant of human factor V that causes a hypercoagulability disorder. In this disorder the Leiden variant of factor V cannot be inactivated by activated protein C. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst Eurasians... mutation |
| 4 points Severe risk factors |
Antiphospholipid syndrome Antiphospholipid syndrome or antiphospholipid antibody syndrome , often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots in both arteries and veins as well as pregnancy-related complications such as... without previous DVT Lupus anticoagulant Lupus anticoagulant is an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane. It is important to note that this disease name is actually a misnomer... |
| Very high risk |
Artificial heart valve An artificial heart valve is a device implanted in the heart of a patient with heart valvular disease. When one of the four heart valves malfunctions, the medical choice may be to replace the natural valve with an artificial valve. This requires open-heart surgery.Valves are integral to the normal... s Antithrombin III deficiency Antithrombin III deficiency is a rare hereditary disorder that generally comes to light when a patient suffers recurrent venous thrombosis and pulmonary embolism... Thrombosis Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss... |
After adding any risk factors together, a total of 1 point or less indicates that no preventive action is needed. A total of 2 points indicates that short-term prophylaxis, e.g. with low molecular weight heparin
Low molecular weight heparin
In medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
, may be used in temporary risk factors, as well as administering prophylactic treatment 7 days postpartum, starting a couple of hours after birth. A total of 3 points increases the necessary duration of postpartum prophylaxis to 6 weeks.
A risk score of 4 points or higher means that there should probably be prophylaxis in the antepartum period, as well as at least 6 weeks postpartum. A previous distal DVT motivates a minimum of 12 weeks (3 months) of therapeutic anticoagulation therapy A previous proximal DVT or pulmonary embolism motivates a minimum of 26 weeks (6.5 months) of therapy If the therapy duration reaches delivery time, the remaining duration may be given postpartum, possibly extending the minimum of 6 weeks postpartum therapy. In a very high risk, there should be a high-dose antepartum prophylaxis, continued at least 12 weeks postpartum.
Women with antiphospholipid syndrome
Antiphospholipid syndrome
Antiphospholipid syndrome or antiphospholipid antibody syndrome , often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots in both arteries and veins as well as pregnancy-related complications such as...
should have an additional low dose prophylactic treatment of Aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
.
Cautions
All anticoagulants (including LMWH) should be used with caution in women with suspected coagulopathyCoagulopathy
Coagulopathy is a condition in which the blood’s ability to clot is impaired. This condition can cause prolonged or excessive bleeding, which may occur spontaneously or following an injury or medical and dental procedures.The normal clotting process depends on the interplay of various proteins in...
, thrombocytopaenia, liver disease
Liver disease
Liver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
and nephropathy
Nephropathy
Nephropathy refers to damage to or disease of the kidney. An older term for this is nephrosis.-Causes:Causes of nephropathy include administration of analgesics, xanthine oxidase deficiency, and long-term exposure to lead or its salts...
.
Major side effects of tinzaparin
Tinzaparin
Tinzaparin is an antithrombotic drug in the heparin group. It is a low molecular weight heparin marketed as Innohep worldwide. It has been approved by the U.S. Food and Drug Administration for once daily treatment and prophylaxis of deep vein thrombosis and pulmonary embolism...
are osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
(occurring in up to 1% of cases), thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
(heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia is the development of thrombocytopenia , due to the administration of various forms of heparin, an anticoagulant...
), haemorrhage, hair loss and drug allergy
Drug allergy
A drug allergy is an allergy to a drug, most commonly a medication. Medical attention should be sought immediately if an allergic reaction is suspected....
. Still, LMWHs are much less likely to cause heparin-induced thrombocytopenia than unfractionated heparin.
Regional anaesthesia
Regional anaesthesia
Regional anaesthesia is anaesthesia affecting only a large part of the body, such as a limb or the lower half of the body. Regional anaesthetic techniques can be divided into central and peripheral techniques. The central techniques include so called neuraxial blocks...
is contraindicated in women on therapeutic anticoagulation, and should not be used within 24 hours of the last dose of tinzaparin.
Monitoring
Anticoagulant therapy with LMWH is not usually monitored. LMWH therapy does not affect the prothrombin timeProthrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...
(PT) or the INR, and Anti Xa levels are not reliable. It can prolong the Partial thromboplastin time
Partial thromboplastin time
The partial thromboplastin time or activated partial thromboplastin time is a performance indicator measuring the efficacy of both the "intrinsic" and the common coagulation pathways...
(APTT) in some women, but still, the APTT is not useful for monitoring.
In order to check for any thrombocytopenia, platelet count should be checked prior to commencing anticoagulant therapy, then 7 to 10 days after commencement, and monthly thereafter. Platelet count should also be checked if unexpected bruising or bleeding occurs.
Reversal
ProtamineProtamine
Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packaging of DNA in spermatozoon than histones, but they must be...
reverses the effect of unfractionated heparin but only partially binds to and reverses LMWH. A dose of 1mg protamine/100IU LMWH reverses 90% of its anti-IIa and 60% of anti-Xa activity, but the clinical effect of the residual anti Xa activity is not known. Both anti-IIa and anti
Xa activity may return up to three hours after protamine reversal, possibly due to release of additional LMWH from depot tissues.
Anticoagulants in breastfeeding
Warfarin, heparin and LMWH do not seem to pass into breast milk, so these are not contraindicated in breastfeedingBreastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
.
Further reading
- http://www.nnuh.nhs.uk/viewdoc.asp?ID=265&t=TrustDoc Therapeutic anticoagulation in pregnancy. Norfolk and Norwich University Hospital (NHS Trust). Reference number CA3017. 9th June 2006 [review June 2009]