Cordocentesis can be performed in utero to determine the platelet count of the fetus. This procedure is only performed if a "prior" pregnancy was affected by . Intrauterine transfusions can be performed during cordocentesis for primary prevention of intracerebral hemorrhage. Any administered cellular blood products must be irradiated to reduce the risk of graft-versus-host disease in the fetus. Additionally, all administered blood products should be reduced-risk ( seronegative and leukoreduced are considered essentially equivalent for the purposes of risk reduction).

If intrauterine platelet transfusions are performed, they are generally repeated weekly (platelet lifespan after transfusion is approximately 8 to 10 days). Platelets administered to the fetus must be negative for the culprit antigen (often -1a, as stated above). Many blood suppliers (such as American Red Cross and United Blood Services) have identified -1a negative donors. An alternative donor is the mother who is, of course, negative for the culprit antigen. However, she must meet general criteria for donation and platelets received from the mother must be washed to remove the offending alloantibody and irradiated to reduce the risk of graft-versus-host disease. If platlet transfusions are needed urgently, incompatible platelets may be used, with the understanding that they may be less effective and that the administration of any blood product carries risk.

The use of Intravenous immunoglobulin () during pregnancy and immediately after birth has been shown to help reduce or alleviate the effects of in infants and reduce the severity of thrombocytopenia. The most common treatment is weekly infusions at a dosage of 1 g/kg beginning at 16 to 28 weeks of pregnancy, depending on the severity of the disease in the previous affected child, and continuing until the birth of the child. In some cases this dosage is increased to 2 g/kg and/or combined with a course of prednisone depending on the exact circumstances of the case. Although this treatment has not been shown to be effective in all cases it has been shown to reduce the severity of thrombocytopenia in some. Also, it is suspected that (though not understood why) provides some added protection from intercranial haemorrhage () to the fetus. Even with treatment, the fetal platelet count may need to be monitored and platelet transfusions may still be required.

The goal of both and platelet transfusion is to avoid hemorrhage. Ultrasound monitoring to detect hemorrhage is not recommended as detection of intracranial hemorrhage generally indicates permanent brain damage (there is no intervention that can be performed to reverse the damage once it has occurred).

Before delivery, the fetal platelet count should be determined. A count of >50,000 μL is recommended for vaginal delivery and the count should be kept above 20,000 μL after birth.

In cases of Rho(D) incompatibility, Rho(D) immunoglobulin is given to prevent sensitization. However, there is no comparable immunotherapy available for other blood group incompatibilities.

Early pregnancy

- IVIG - IVIG stands for Intravenous Immunoglobulin. It is used in cases of previous loss, high maternal titers, known aggressive antibodies, and in cases where religion prevents blood transfusion. Ivig can be more effective than IUT alone. Fetal mortality was reduced by 36% in the IVIG and IUT group than in the IUT alone group. IVIG and plasmapheresis together can reduce or eliminate the need for an IUT.

- Plasmapheresis - Plasmapheresis aims to decrease the maternal titer by direct plasma replacement. Plasmapheresis and IVIG together can even be used on women with previously hydropic fetuses and losses.

Mid to late pregnancy

- IUT - Intrauterine Transfusion (IUT) is done either by intraperitoneal transfusion (IPT) or intravenous transfusion (IVT). IVT is preferred over IPT. IUTs are only done until 35 weeks. After that, the risk of an IUT is greater than the risk from post birth transfusion.

- Steroids - Steroids are sometimes given to the mother before IUTs and early delivery to mature the fetal lungs.

- Phenobarbital - Phenobarbital is sometimes given to the mother to help mature the fetal liver and reduce hyperbilirubinemia.

- Early Delivery - Delivery can occur anytime after the age of viability. Emergency delivery due to failed IUT is possible, along with induction of labor at 35–38 weeks.

Rhesus-negative mothers who have had a pregnancy who are pregnant with a rhesus-positive infant are offered Rho(D) immune globulin (RhIG) at 28 weeks during pregnancy, at 34 weeks, and within 48 hours after delivery to prevent sensitization to the D antigen. It works by binding any fetal red blood cells with the D antigen before the mother is able to produce an immune response and form anti-D IgG. A drawback to pre-partum administration of RhIG is that it causes a positive antibody screen when the mother is tested, which can be difficult to distinguish from natural immunological responses that result in antibody production. Without Rho(D) immunoglobulin, the risk of isoimmunization is approximately 17%; with proper administration the risk is reduced to less than 0.1-0.2%.

After birth, treatment depends on the severity of the condition, but could include temperature stabilization and monitoring, phototherapy, transfusion with compatible packed red blood, exchange transfusion with a blood type compatible with both the infant and the mother, sodium bicarbonate for correction of acidosis and/or assisted ventilation.

- Phototherapy - Phototherapy is used for cord bilirubin of 3 or higher. Some doctors use it at lower levels while awaiting lab results.

- IVIG - IVIG has been used to successfully treat many cases of HDN. It has been used not only on anti-D, but on anti-E as well. IVIG can be used to reduce the need for exchange transfusion and to shorten the length of phototherapy. The AAP recommends "In isoimmune hemolytic disease, administration of intravenousγ-globulin (0.5-1 g/kg over 2 hours) is recommended if the TSB is rising despite intensive phototherapy or the TSB level is within 2 to 3 mg/dL (34-51 μmol/L) of the exchange level . If necessary, this dose can be repeated in 12 hours (evidence quality B: benefits exceed harms). Intravenous γ-globulin has been shown to reduce the need for exchange transfusions in Rh and ABO hemolytic disease."

- Exchange transfusion - Exchange transfusion is used when bilirubin reaches either the high or medium risk lines on the nonogram provided by the American Academy of Pediatrics (Figure 4). Cord bilirubin >4 is also indicative of the need for exchange transfusion.

The antibodies in ABO HDN cause anemia due to destruction of fetal red blood cells and jaundice due to the rise in blood levels of bilirubin a by-product of hemoglobin break down. If the anemia is severe, it can be treated with a blood transfusion, however this is rarely needed. On the other hand, neonates have underdeveloped livers that are unable to process large amounts of bilirubin and a poorly developed blood-brain barrier that is unable to block bilirubin from entering the brain.This can result in kernicterus if left unchecked. If the bilirubin level is sufficiently high as to cause worry, it can be lowered via phototherapy in the first instance or an exchange transfusion if severely elevated.

- Phototherapy - Phototherapy is used for cord bilirubin of 3 or higher. Some doctors use it at lower levels while awaiting lab results.

- IVIG - IVIG has been used to successfully treat many cases of HDN. It has been used not only on anti-D, but on anti-E as well. IVIG can be used to reduce the need for exchange transfusion and to shorten the length of phototherapy. The AAP recommends "In isoimmune hemolytic disease, administration of intravenousγ-globulin (0.5-1 g/kg over 2 hours) is recommended if the TSB is rising despite intensive phototherapy or the TSB level is within 2 to 3 mg/dL (34-51 μmol/L) of the exchange level . If necessary, this dose can be repeated in 12 hours (evidence quality B: benefits exceed harms). Intravenous γ-globulin has been shown to reduce the need for exchange transfusions in Rh and ABO hemolytic disease."

- Exchange transfusion - Exchange transfusion is used when bilirubin reaches either the high or medium risk lines on the normogram provided by the American Academy of Pediatrics (Figure 4). Cord bilirubin >4 is also indicative of the need for exchange transfusion.

Recombinant EPO (r-EPO) may be given to premature infants to stimulate red blood cell production. Brown and Keith (1999) studied two groups of 40 very low birth weight (VLBW) infants to compare the erythropoietic response between two and five times a week dosages of recombinant human erythropoietin (r-EPO) using the same dose. They established that more frequent dosing of the same weekly amount of r-EPO generated a significant and continuous increase in Hb in VLBW infants. The infants that received five dosages had 219,857 mm³ while infants that received two dosages only had 173,361 mm³. However, the response to r-EPO typically takes up to two weeks and the higher dosages lead to higher Hb. Brown and Keith (1999) study also showed responses between two dosage schedules (two times a week and five times a week). Infants were recruited for gestational age—age since conception—≤27 weeks and 28 to 30 weeks and then randomized into the two groups, each totaling 500 U/kg a week. Brown and Keith found that after two weeks of r-EPO administration, Hb counts had increased and leveled off; the infants who received r-EPO five times a week had significantly higher Hb counts. This was present at four weeks for all infants ≤30 weeks gestation and at 8 weeks for infants ≤27 weeks gestation.

To date, studies of r-EPO use in premature infants have had mixed results. Ohls et al. examined the use of early r-EPO plus iron and found no short-term benefits in two groups of infants (172 infants less than 1000 g and 118 infants 1000–1250 g). All r-EPO treated infants received 400 U/g three times a week until they reached 35 weeks gestational age. The use of r-EPO did not decrease the average number of transfusions in the infants born at less than 1000 g, or the percentage of infants in the 1000 to 1250 group. A multi-center European trial studied early versus late r-EPO in 219 infants with birth weights between 500 and 999 g. An r-EPO close of 750 U/kg/week was given to infants in both the early (1–9 weeks) and late (4–10 weeks) groups. The two r-EPO groups were compared to a control group who did not receive r-EPO. Infants in all three groups received 3 to 9 mg/kg of enteral iron. These investigators reported a slight decrease in transfusion and donor exposures in the early r-EPO group (1–9 weeks): 13% early, 11% late and 4% control group. It is likely that only a carefully selected subpopulation of infants may benefit from its use. Contrary to what just said, Bain and Blackburn (2004) also state in another study the use of r-EPO does not appear to have a significant effect on reducing the numbers of early transfusions in most infants, but may be useful to reduce numbers of late transfusion in extremely low-birth-weight infants. A British task force to establish transfusion guidelines for neonates and young children and to help try to explain this confusion recently concluded that “the optimal dose, timing, and nutritional support required during EPO treatment has yet to be defined and currently the routine use of EPO in this patient population is not recommended as similar reduction in blood use can probably be achieved with appropriate transfusion protocols.”

Other strategies involve the reduction of blood loss during phlebotomy.

Another treatment used is therapeutic strategies. These strategies are aimed at reducing transfusions have assessed the use of strict blood transfusions guidelines and EPO therapy, but reduction of blood loss is most important. For extremely low birth weight infants, laboratory blood testing using bedside devices offers a unique opportunity to reduce blood transfusions. This practice has been referred to as point-of-care testing. Use of these kind of devices to measure the most common ordered blood tests could significantly decrease phlebotomy loss and lead to a reduction in the need for blood transfusions among critically ill premature neonates. A study was done by Adams, Benitz, Geaghan, Kumar, Madan and Widness (2005) to test this theory by conducting a retrospective chart review on all inborn infants <1000g admitted to the NICU during two separate years. Conventional bench top laboratory analysis during the first year was done using Radiometer Blood Gas and Electrolyte Analyzer. Bedside blood gas analysis during the second year was performed using a point-of-care analyzer. An estimated blood loss in the two groups was determined based on the number of specific blood tests on individual infants. The study found that there was an estimated 30% reduction in the total volume of blood removed for the blood tests. This study concluded that there is modern technology that can be used instead of blood transfusions and r-EPO.

Immune thrombocytopenic purpura (), sometimes called idiopathic thrombocytopenic purpura is a condition in which autoantibodies are directed against a patient's own platelets, causing platelet destruction and thrombocytopenia. Anti-platelet autoantibodies in a pregnant woman with immune thrombocytopenic purpura will attack the patient's own platelets and will also cross the placenta and react against fetal platelets. Therefore, is a significant cause of fetal and neonatal immune thrombocytopenia. Approximately 10% of newborns affected by will have platelet counts <50,000 μL and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with .

Mothers with thrombocytopenia or a previous diagnosis of should be tested for serum antiplatelet antibodies. A woman with symptomatic thrombocytopenia and an identifiable antiplatelet antibody should be started on therapy for their which may include steroids or . Fetal blood analysis to determine the platelet count is not generally performed as -induced thrombocytopenia in the fetus is generally less severe than . Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia.

Treatment of DIC is centered around treating the underlying condition. Transfusions of platelets or fresh frozen plasma can be considered in cases of significant bleeding, or those with a planned invasive procedure. The target goal of such transfusion depends on the clinical situation. Cryoprecipitate can be considered in those with a low fibrinogen level.

Treatment of thrombosis with anticoagulants such as heparin is rarely used due to the risk of bleeding.

Recombinant human activated protein C was previously recommended in those with severe sepsis and DIC, but drotrecogin alfa has been shown to confer no benefit and was withdrawn from the market in 2011.

Recombinant factor VII has been proposed as a "last resort" in those with severe hemorrhage due to obstetric or other causes, but conclusions about its use are still insufficient.

For patients with vWD type 1 and vWD type 2A, desmopressin is available as different preparations, recommended for use in cases of minor trauma, or in preparation for dental or minor surgical procedures. Desmopressin stimulates the release of vWF from the Weibel-Palade bodies of endothelial cells, thereby increasing the levels of vWF (as well as coagulant factor VIII) three- to five-fold. Desmopressin is also available as a preparation for intranasal administration (Stimate) and as a preparation for intravenous administration. Recently, the FDA has approved the use of Baxalta’s Vonvendi. This is the first recombinant form of vWF. The effectiveness of this treatment is different than desmopressin because it only contains vWF, not vWF with the addition of FVIII. This treatment is only recommended for use by individuals who are 18 years of age or older.

Desmopressin is contraindicated in vWD type 2b because of the risk of aggravated thrombocytopenia and thrombotic complications. Desmopressin is probably not effective in vWD type 2M and is rarely effective in vWD type 2N. It is totally ineffective in vWD type 3.

For women with heavy menstrual bleeding, estrogen-containing oral contraceptive medications are effective in reducing the frequency and duration of the menstrual periods. Estrogen and progesterone compounds available for use in the correction of menorrhagia are ethinylestradiol and levonorgestrel (Levona, Nordette, Lutera, Trivora). Administration of ethinylestradiol diminishes the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, leading to stabilization of the endometrial surface of the uterus.

Desmopressin is a synthetic analog of the natural antidiuretic hormone vasopressin. Its overuse can lead to water retention and dilutional hyponatremia with consequent convulsion.

For patients with vWD scheduled for surgery and cases of vWD disease complicated by clinically significant hemorrhage, human-derived medium purity factor VIII concentrates, which also contain von Willebrand factors, are available for prophylaxis and treatment. Humate P, Alphanate, Wilate and Koate HP are commercially available for prophylaxis and treatment of vWD. Monoclonally purified factor VIII concentrates and recombinant factor VIII concentrates contain insignificant quantity of vWF, so are not clinically useful.

Development of alloantibodies occurs in 10-15% of patients receiving human-derived medium-purity factor VIII concentrates and the risk of allergic reactions including anaphylaxis must be considered when administering these preparations. Administration of the latter is also associated with increased risk of venous thromboembolic complications.

Blood transfusions are given as needed to correct anemia and hypotension secondary to hypovolemia. Infusion of platelet concentrates is recommended for correction of hemorrhage associated with platelet-type vWD.

The antifibrinolytic agents epsilon amino caproic acid and tranexamic acid are useful adjuncts in the management of vWD complicated by clinical hemorrhage. The use topical thrombin JMI and topical Tisseel VH are effective adjuncts for correction of hemorrhage from wounds.

Once a woman has antibodies, she is at high risk for a transfusion reaction. For this reason, she must carry a medical alert card at all times and inform all doctors of her antibody status.

"Acute hemolytic transfusion reactions may be either immune-mediated or nonimmune-mediated. Immune-mediated hemolytic transfusion reactions caused by immunoglobulin M (IgM) anti-A, anti-B, or anti-A,B typically result in severe, potentially fatal complement-mediated intravascular hemolysis. Immune-mediated hemolytic reactions caused by IgG, Rh, Kell, Duffy, or other non-ABO antibodies typically result in extravascular sequestration, shortened survival of transfused red cells, and relatively mild clinical reactions. Acute hemolytic transfusion reactions due to immune hemolysis may occur in patients who have no antibodies detectable by routine laboratory procedures"

Summary of transfusion reactions in the US

Most Rh disease can be prevented by treating the mother during pregnancy or promptly (within 72 hours) after childbirth. The mother has an intramuscular injection of anti-Rh antibodies (Rho(D) immune globulin). This is done so that the fetal rhesus D positive erythrocytes are destroyed before the immune system of the mother can discover them and become sensitized. This is passive immunity and the effect of the immunity will wear off after about 4 to 6 weeks (or longer depending on injected dose) as the anti-Rh antibodies gradually decline to zero in the maternal blood.

It is part of modern antenatal care to give all rhesus D negative pregnant women an anti-RhD IgG immunoglobulin injection at about 28 weeks gestation (with or without a booster at 34 weeks gestation). This reduces the effect of the vast majority of sensitizing events which mostly occur after 28 weeks gestation. Giving Anti-D to all Rhesus negative pregnant women can mean giving it to mothers who do not need it (because her baby is Rhesus negative or their blood did not mix). Many countries routinely give Anti-D to Rhesus D negative women in pregnancy. In other countries, stocks of Anti-D can run short or even run out. Before Anti-D is made routine in these countries, stocks should be readily available so that it is available for women who need Anti-D in an emergency situation.

A recent review found research into giving Anti-D to all Rhesus D negative pregnant women is of low quality. However the research did suggest that the risk of the mother producing antibodies to attack Rhesus D positive fetal cells was lower in mothers who had the Anti-D in pregnancy. There were also fewer mothers with a positive kleihauer test (which shows if the mother’s and unborn baby’s blood has mixed).

Anti-RhD immunoglobulin is also given to non-sensitized rhesus negative women immediately (within 72 hours—the sooner the better) after potentially sensitizing events that occur earlier in pregnancy.

The discovery of cell-free DNA in the maternal plasma has allowed for the non-invasive determination of the fetal RHD genotype. In May 2017, the Society for Obstetrics and Gynecology of Canada is now recommending that the optimal management of the D-negative pregnant woman is based on the prediction of the fetal D-blood group by cell-free DNA in maternal plasma with targeted antenatal anti-D prophylaxis. This provides the optimal care for D-negative pregnant women and has been adopted as the standard approach in a growing number of countries around the world. It is no longer considered appropriate to treat all D-negative pregnant women with human plasma derivatives when there are no benefits to her or to the fetus in a substantial percentage of cases.

There are several intervention options available in early, mid and late pregnancies.

There is no specific treatment for thrombophilia, unless it is caused by an underlying medical illness (such as nephrotic syndrome), where the treatment of the underlying disease is needed. In those with unprovoked and/or recurrent thrombosis, or those with a high-risk form of thrombophilia, the most important decision is whether to use anticoagulation medications, such as warfarin, on a long-term basis to reduce the risk of further episodes. This risk needs to weighed against the risk that the treatment will cause significant bleeding, as the reported risk of major bleeding is over 3% per year, and 11% of those with major bleeding may die as a result.

Apart from the abovementioned forms of thrombophilia, the risk of recurrence after an episode of thrombosis is determined by factors such as the extent and severity of the original thrombosis, whether it was provoked (such as by immobilization or pregnancy), the number of previous thrombotic events, male sex, the presence of an inferior vena cava filter, the presence of cancer, symptoms of post-thrombotic syndrome, and obesity. These factors tend to be more important in the decision than the presence or absence of a detectable thrombophilia.

Those with antiphospholipid syndrome may be offered long-term anticoagulation after a first unprovoked episode of thrombosis. The risk is determined by the subtype of antibody detected, by the antibody titer (amount of antibodies), whether multiple antibodies are detected, and whether it is detected repeatedly or only on a single occasion.

Women with a thrombophilia who are contemplating pregnancy or are pregnant usually require alternatives to warfarin during pregnancy, especially in the first 13 weeks, when it may produce abnormalities in the unborn child. Low molecular weight heparin (LMWH, such as enoxaparin) is generally used as an alternative. Warfarin and LMWH may safely be used in breastfeeding.

When women experience recurrent pregnancy loss secondary to thrombophilia, some studies have suggested that low molecular weight heparin reduces the risk of miscarriage. When the results of all studies are analysed together, no statistically signifiant benefit could be demonstrated.

Blood transfusions in those without symptoms is not recommended until the hemoglobin is below 60 to 80 g/L (6 to 8 g/dL). In those with coronary artery disease who are not actively bleeding transfusions are only recommended when the hemoglobin is below 70 to 80g/L (7 to 8 g/dL). Transfusing earlier does not improve survival. Transfusions otherwise should only be undertaken in cases of cardiovascular instability.

In cases where oral iron has either proven ineffective, would be too slow (for example, pre-operatively) or where absorption is impeded (for example in cases of inflammation), parenteral iron can be used. The body can absorb up to 6 mg iron daily from the gastrointestinal tract. In many cases the patient has a deficit of over 1,000 mg of iron which would require several months to replace. This can be given concurrently with erythropoietin to ensure sufficient iron for increased rates of erythropoiesis.

In ABO hemolytic disease of the newborn (also known as ABO HDN) maternal IgG antibodies with specificity for the ABO blood group system pass through the placenta to the fetal circulation where they can cause hemolysis of fetal red blood cells which can lead to fetal anemia and HDN. In contrast to Rh disease, about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies.

The ABO blood group system is the best known surface antigen system, expressed on a wide variety of human cells. For Caucasian populations about one fifth of all pregnancies have ABO incompatibility between the fetus and the mother, but only a very small minority develop symptomatic ABO HDN. The latter typically only occurs in mothers of blood group O, because they can produce enough IgG antibodies to cause hemolysis.

Although very uncommon, cases of ABO HDN have been reported in infants born to mothers with blood groups A and B.

Plasmapheresis may be used to decrease viscosity in the case of myeloma, whereas leukapheresis or phlebotomy may be employed in a leukemic or polycythemic crisis, respectively. Blood transfusions should be used with caution as they can increase serum viscosity. Hydration is a temporizing measure to employ while preparing pheresis. Even after treatment, the condition will recur unless the underlying disorder is treated.

Acquired hemolytic anemia can be divided into immune and non-immune mediated forms of hemolytic anemia.

Rh disease (also known as rhesus isoimmunisation, Rh (D) disease, rhesus incompatibility, rhesus disease, RhD hemolytic disease of the newborn, rhesus D hemolytic disease of the newborn or RhD HDN) is a type of hemolytic disease of the newborn (HDN). The disease ranges from mild to severe, and typically occurs only in some second or subsequent pregnancies of Rh negative women where the fetus's father is Rh positive, leading to a Rh+ pregnancy. During birth, the mother may be exposed to the infant's blood, and this causes the development of antibodies, which may affect the health of subsequent Rh+ pregnancies. In mild cases, the fetus may have mild anaemia with reticulocytosis. In moderate or severe cases the fetus may have a more marked anaemia and erythroblastosis fetalis (hemolytic disease of the newborn). When the disease is very severe it may cause hydrops fetalis or stillbirth.

Rh disease is generally preventable by treating the mother during pregnancy or soon after delivery with an intramuscular injection of anti-RhD immunoglobulin (Rho(D) immune globulin). The RhD protein is coded by the RHD gene.

Drug induced hemolysis has large clinical relevance. It occurs when drugs actively provoke red blood cell destruction. It can be divided in the following manner:

- Drug-induced autoimmune hemolytic anemia

- Drug-induced nonautoimmune hemolytic anemia

A total of four mechanisms are usually described, but there is some evidence that these mechanisms may overlap.

Neonatal infection treatment is typically started before the diagnosis of the cause can be confirmed.

Neonatal infection can be prophylactically treated with antibiotics. Maternal treatment with antibiotics is primarily used to protect against group B streptococcus.

Women with a history of HSV, can be treated with antiviral drugs to prevent symptomatic lesions and viral shedding that could infect the infant at birth. The antiviral medications used include acyclovir, penciclovir, valacyclovir, and famciclovir. Only very small amounts of the drug can be detected in the fetus. There are no increases in drug-related abnormalities in the infant that could be attributed to acyclovir. Long-term effects of antiviral medications have not been evaluated for their effects after growth and development of the child occurs. Neutropenia can be a complication of acyclovir treatment of neonatal HSV infection, but is usually transient. Treatment with immunoglobulin therapy has not been proven to be effective.

Prognosis varies depending on the underlying disorder, and the extent of the intravascular thrombosis (clotting). The prognosis for those with DIC, regardless of cause, is often grim: Between 20% and 50% of patients will die. DIC with sepsis (infection) has a significantly higher rate of death than DIC associated with trauma.

There are divergent views as to whether everyone with an unprovoked episode of thrombosis should be investigated for thrombophilia. Even those with a form of thrombophilia may not necessarily be at risk of further thrombosis, while recurrent thrombosis is more likely in those who have had previous thrombosis even in those who have no detectable thrombophilic abnormalities. Recurrent thromboembolism, or thrombosis in unusual sites (e.g. the hepatic vein in Budd-Chiari syndrome), is a generally accepted indication for screening. It is more likely to be cost-effective in people with a strong personal or family history of thrombosis. In contrast, the combination of thrombophilia with other risk factors may provide an indication for preventative treatment, which is why thrombophilia testing may be performed even in those who would not meet the strict criteria for these tests. Searching for a coagulation abnormality is not normally undertaken in patients in whom thrombosis has an obvious trigger. For example, if the thrombosis is due to immobilization after recent orthopedic surgery, it is regarded as "provoked" by the immobilization and the surgery and it is less likely that investigations will yield clinically important results.

When venous thromboembolism occurs when a patient is experiencing transient major risk factors such as prolonged immobility, surgery, or trauma, testing for thrombophilia is not appropriate because the outcome of the test would not change a patient's indicated treatment. In 2013, the American Society of Hematology, as part of recommendations in the Choosing Wisely campaign, cautioned against overuse of thrombophilia screening; false positive results of testing would lead to people inappropriately being labeled as having thrombophilia, and being treated with anticoagulants without clinical need

In the United Kingdom, professional guidelines give specific indications for thrombophilia testing. It is recommended that testing be done only after appropriate counseling, and hence the investigations are usually not performed at the time when thrombosis is diagnosed but at a later time. In particular situations, such as retinal vein thrombosis, testing is discouraged altogether because thrombophilia is not regarded as a major risk factor. In other rare conditions generally linked with hypercoagulability, such as cerebral venous thrombosis and portal vein thrombosis, there is insufficient data to state for certain whether thrombophilia screening is helpful, and decisions on thrombophilia screening in these conditions are therefore not regarded as evidence-based. If cost-effectiveness (quality-adjusted life years in return for expenditure) is taken as a guide, it is generally unclear whether thrombophilia investigations justify the often high cost, unless the testing is restricted to selected situations.

Recurrent miscarriage is an indication for thrombophilia screening, particularly antiphospholipid antibodies (anti-cardiolipin IgG and IgM, as well as lupus anticoagulant), factor V Leiden and prothrombin mutation, activated protein C resistance and a general assessment of coagulation through an investigation known as thromboelastography.

Women who are planning to use oral contraceptives do not benefit from routine screening for thrombophilias, as the absolute risk of thrombotic events is low. If either the woman or a first-degree relative has suffered from thrombosis, the risk of developing thrombosis is increased. Screening this selected group may be beneficial, but even when negative may still indicate residual risk. Professional guidelines therefore suggest that alternative forms of contraception be used rather than relying on screening.

Thrombophilia screening in people with arterial thrombosis is generally regarded unrewarding and is generally discouraged, except possibly for unusually young patients (especially when precipitated by smoking or use of estrogen-containing hormonal contraceptives) and those in whom revascularization, such as coronary arterial bypass, fails because of rapid occlusion of the graft.

The treatment of CMML remains challenging due to the lack of clinical trials investigating the disease as its own clinical entity. It is often grouped with MDS in clinical trials, and for this reason the treatment of CMML is very similar to that of MDS. Most cases are dealt with as supportive rather than curative because most therapies do not effectively increase survival. Indications for treatment include the presence of B symptoms, symptomatic organ involvement, increasing blood counts, hyperleukocytosis, leukostasis and/or worsening cytopaenias.

Blood transfusions and EPO administration are used to raise haemoglobin levels in cases with anaemia.

Azacitidine is a drug approved by the US Food & Drug Administration (FDA) for the treatment of CMML and by the European Medicines Agency for high risk non-proliferative CMML with 10-19% marrow blasts. It is a cytidine analogue that causes hypomethylation of DNA by inhibition of DNA methyltransferase. Decitabine is a similar drug to azacitidine and is approved by the FDA for treatments of all subtypes of MDS, including CMML. Hydroxyurea is a chemotherapy that is used in the myeloproliferative form of CMML to reduce cell numbers.

Haematopoietic stem cell transplant remains the only curative treatment for CMML. However, due to the late age of onset and presence of other illnesses, this form of treatment is often not possible.

Acquired vWD can occur in patients with autoantibodies. In this case, the function of vWF is not inhibited, but the vWF-antibody complex is rapidly cleared from the circulation.

A form of vWD occurs in patients with aortic valve stenosis, leading to gastrointestinal bleeding (Heyde's syndrome). This form of acquired vWD may be more prevalent than is presently thought. In 2003, Vincentelli "et al." noted that patients with acquired vWD and aortic stenosis who underwent valve replacement experienced a correction of their hemostatic abnormalities, but that the hemostatic abnormalities can recur after 6 months when the prosthetic valve is a poor match with the patient.

Similarly, acquired vWD contributes to the bleeding tendency in people with an implant of a left ventricular assist device (a pump that pumps blood from the left ventricle of the heart into the aorta). Large multimers of vWF are destroyed by mechanical stress in both conditions.

Thrombocythemia is another cause of acquired von Willebrand disease, due to sequestration of vWF via the adhesion of vast numbers of platelets. Acquired vWD has also been described in Wilms' tumour, hypothyroidism, and placental mesenchymal dysplasias.