Individuals experiencing episodic bleeding as a result of congenital dysfibrinogenemia should be treated at a center specialized in treating hemophilia. They should avoid all medications that interfere with normal platelet function. During bleeding episodes, treatment with fibrinogen concentrates or in emergencies or when these concentrates are unavailable, infusions of fresh frozen plasma and/or cryoprecipitate (a fibrinogen-rich plasma fraction) to maintain fibrinogen activity levels >1 gram/liter. Tranexamic acid or fibrinogen concentrates are recommended for prophylactic treatment prior to minor surgery while fibrinogen concentrates are recommended prior to major surgery with fibrinogen concentrates usage seeking to maintain fibrinogen activity levels at >1 gram/liter. Women undergoing vaginal or Cesarean child birth should be treated at a hemophilia center with fibrinogen concentrates to maintain fibrinogen activity levels at 1.5 gram/liter. The latter individuals require careful observation for bleeding during their post-partum periods.

Individuals experiencing episodic thrombosis as a result of congenital dysfibrinogenemia should also be treated at a center specialized in treating hemophilia using antithrombotic agents. They should be instructed on antithrombotic behavioral methods fur use in high risk situations such as long car rides and air flights. Venous thrombosis should be treated with low molecular weight heparin for a period that depends on personal and family history of thrombosis events. Prophylactic treatment prior to minor surgery should avoid fibrinogen supplementation and use prophylactic anticoagulation measures; prior to major surgery, fibrinogen supplementation should be used only if serious bleeding occurs; otherwise, prophylactic anticoagulation measures are recommended.

Therapy involves both preventive measures and treatment of specific bleeding episodes.

- Dental hygiene lessens gingival bleeding

- Avoidance of antiplatelet agents such as aspirin and other anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, and anticoagulants

- Iron or folate supplementation may be necessary if excessive or prolonged bleeding has caused anemia

- Hepatitis B vaccine

- Antifibrinolytic drugs such as tranexamic acid or ε-aminocaproic acid (Amicar)

- Desmopressin (DDAVP) does not normalize the bleeding time in Glanzmann's thrombasthenia but anecdotally improves hemostasis

- Hormonal contraceptives to control excessive menstrual bleeding

- Topical agents such as gelfoam, fibrin sealants, polyethylene glycol polymers, custom dental splints

- Platelet transfusions (only if bleeding is severe; risk of platelet alloimmunization)

- Recombinant factor VIIa, AryoSeven or NovoSeven FDA approved this drug for the treatment of the disease on July 2014.

- Hematopoietic stem cell transplantation (HSCT) for severe recurrent hemorrhages

Treatment of asymptomatic congenital dysfibrinogenemia depends in part on the expectations of developing bleeding and/or thrombotic complications as estimated based on the history of family members with the disorder and, where available, determination of the exact mutation causing the disorder plus the propensity of the particular mutation type to develop these complications. In general, individuals with this disorder require regular follow-up and multidiscipline management prior to surgery, pregnancy, and giving childbirth. Women with the disorder appear to have an increased rate of miscarriages and all individuals with fibrinogen activity in clotting tests below 0.5 grams/liter are prone to bleeding and spontaneous abortions. Women with multiple miscarriages and individuals with excessively low fibrinogen activity levels should be considered for prophylaxis therapy with fibrinogen replacement during pregnancy, delivery, and/or surgery.

Given the fact that HIT predisposes strongly to new episodes of thrombosis, it is not sufficient to simply discontinue the heparin administration. Generally, an alternative anticoagulant is needed to suppress the thrombotic tendency while the generation of antibodies stops and the platelet count recovers. To make matters more complicated, the other most commonly used anticoagulant, warfarin, should not be used in HIT until the platelet count is at least 150 x 10^9/L because there is a very high risk of warfarin necrosis in people with HIT who have low platelet counts. Warfarin necrosis is the development of skin gangrene in those receiving warfarin or a similar vitamin K inhibitor. If the patient was receiving warfarin at the time when HIT is diagnosed, the activity of warfarin is reversed with vitamin K. Transfusing platelets is discouraged, as there is a theoretical risk that this may worsen the risk of thrombosis; the platelet count is rarely low enough to be the principal cause of significant hemorrhage.

Various non-heparin agents are used to provide anticoagulation in those with strongly suspected or proven HIT: danaparoid, fondaparinux, bivalirudin and argatroban. These are alternatives to heparin therapy. Not all agents are available in all countries, and not all are approved for this specific use. For instance, argatroban is only recently licensed in the United Kingdom, and danaparoid is not available in the United States. Fondaparinux, a Factor Xa inhibitor, is commonly used off label for HIT treatment in the United States.

According to a systematic review, people with HIT treated with lepirudin showed a relative risk reduction of clinical outcome (death, amputation, etc.) to be 0.52 and 0.42 when compared to patient controls. In addition, people treated with argatroban for HIT showed a relative risk reduction of the above clinical outcomes to be 0.20 and 0.18. Lepirudin production stopped on May 31, 2012.

In terms of treatment/management, bleeding events can be controlled by platelet transfusion.

Most heterozygotes, with few exceptions, do not have a bleeding diathesis. BSS presents as a bleeding disorder due to the inability of platelets to bind and aggregate at sites of vascular endothelial injury. In the event of an individual with mucosal bleeding tranexamic acid can be given.

The affected individual may need to avoid contact sports and medications such as aspirin, which can increase the possibility of bleeding. A potential complication is the possibility of the individual producing antiplatelet antibodies

There has been no general recommendation for treatment of patients with Giant Platelet Disorders, as there are many different specific classifications to further categorize this disorder which each need differing treatments. Platelet transfusion is the main treatment for people presenting with bleeding symptoms. There have been experiments with DDAVP (1-deamino-8-arginine vasopressin) and splenectomy on people with Giant platelet disorders with mixed results, making this type of treatment contentious.

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.

As there is no cure, treatment is focused on prevention of thrombotic complications by counseling. In addition, temporary treatment with an anticoagulant may be required during periods of particularly high risk of thrombosis, such as major surgery.

Studies have found that about 5 percent of Caucasians in North America have factor V Leiden. The condition is less common in Latin Americans and African-Americans and is extremely rare in people of Asian descent.

Up to 30 percent of patients who present with deep vein thrombosis (DVT) or pulmonary embolism have this condition. The risk of developing a clot in a blood vessel depends on whether a person inherits one or two copies of the factor V Leiden mutation. Inheriting one copy of the mutation from a parent (heterozygous) increases by fourfold to eightfold the chance of developing a clot. People who inherit two copies of the mutation (homozygous), one from each parent, may have up to 80 times the usual risk of developing this type of blood clot. Considering that the risk of developing an abnormal blood clot averages about 1 in 1,000 per year in the general population, the presence of one copy of the factor V Leiden mutation increases that risk to between 4 in 1,000 to 8 in 1,000. Having two copies of the mutation may raise the risk as high as 80 in 1,000. It is unclear whether these individuals are at increased risk for "recurrent" venous thrombosis. While only 1 percent of people with factor V Leiden have two copies of the defective gene, these homozygous individuals have a more severe clinical condition. The presence of acquired risk factors for venous thrombosis—including smoking, use of estrogen-containing (combined) forms of hormonal contraception, and recent surgery—further increase the chance that an individual with the factor V Leiden mutation will develop DVT.

Women with factor V Leiden have a substantially increased risk of clotting in pregnancy (and on estrogen-containing birth control pills or hormone replacement) in the form of deep vein thrombosis and pulmonary embolism. They also may have a small increased risk of preeclampsia, may have a small increased risk of low birth weight babies, may have a small increased risk of miscarriage and stillbirth due to either clotting in the placenta, umbilical cord, or the fetus (fetal clotting may depend on whether the baby has inherited the gene) or influences the clotting system may have on placental development. Note that many of these women go through one or more pregnancies with no difficulties, while others may repeatedly have pregnancy complications, and still others may develop clots within weeks of becoming pregnant.

For people who have severe congenital protein C deficiency, protein C replacement therapies are available, which is indicated and approved for use in the United States and Europe for the prevention of purpura fulminans. Protein C replacement is often in combination with anticoagulation therapy of injectable low molecular weight heparin or oral warfarin. Before initiating warfarin therapy, a few days of therapeutic heparin may be administered to prevent warfarin skin necrosis and other progressive or recurrent thrombotic complications.

There are too few cases of fibrinogen storage disease to establish optimal treatments for the liver diseases. Management of the disorder has been based on general recommendations for patients with liver disease, particularly Alpha 1 antitrypsin deficiency-associated liver disease. In the latter disease, autophagy, the pathway that cells use to dispose of dysfunctional or excessively stored components including proteins, has been targeted using autophagy-enhancing drugs, e.g. carbamazepine, vitamin E, and ursodeoxycholic acid. These drugs have been tested in individual patients with fibrin storage disease with some success in reducing evidence of liver injure, i.e. reduction in blood liver enzyme levels. These and other autophagy-enhancing drugs are suggested to be further studied in fibrinogen storage disease.

Hydroxycarbamide and anagrelide are contraindicated during pregnancy and nursing. Essential thrombocytosis can be linked with a three-fold increase in risk of miscarriage. Throughout pregnancy, close monitoring of the mother and fetus is recommended. Low-dose low molecular weight heparin (e.g. enoxaparin) may be used. For life-threatening complications, the platelet count can be reduced rapidly using platelet apheresis, a procedure that removes platelets from the blood and returns the remainder to the patient.

In people without a detectable thrombophilia, the cumulative risk of developing thrombosis by the age of 60 is about 12%. About 60% of people who are deficient in antithrombin will have experienced thrombosis at least once by age 60, as will about 50% of people with protein C deficiency and about a third of those with protein S deficiency. People with activated protein C resistance (usually resulting from factor V Leiden), in contrast, have a slightly raised absolute risk of thrombosis, with 15% having had at least one thrombotic event by the age of sixty. In general, men are more likely than women to experience repeated episodes of venous thrombosis.

People with factor V Leiden are at a relatively low risk of thrombosis, but may develop thrombosis in the presence of an additional risk factor, such as immobilization. Most people with the prothrombin mutation (G20210A) never develop thrombosis.

The course of treatment and the success rate is dependent on the type of TMA. Some patients with atypical HUS and TTP have responded to plasma infusions or exchanges, a procedure which replaces proteins necessary for the complement cascade that the patient does not have; however, this is not a permanent solution or treatment, especially for patients with congenital predispositions.

The amount of fresh frozen plasma required to reverse disseminated intravascular coagulation associated with purpura fulminans may lead to complications of fluid overload and death, especially in neonates, such as transfusion-related acute lung injury. Exposure to multiple plasma donors over time increases the cumulative risk for transfusion-associated viral infection and allergic reaction to donor proteins found in fresh frozen plasma.

Allergic reactions and alloantibody formation are also potential complications, as with any protein replacement therapy.

Concomitant warfarin therapy in subjects with congenital protein C deficiency is associated with an increased risk of warfarin skin necrosis.

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.

The exact number of cases of HIT in the general population is unknown. What is known is that women receiving heparin after a recent surgical procedure, particularly cardiothoracic surgery, have a higher risk, while the risk is very low in women just before and after giving birth. Some studies have shown that HIT is less common in those receiving low molecular weight heparin.

Due to the high mortality of untreated TTP, a presumptive diagnosis of TTP is made even when only microangiopathic hemolytic anemia and thrombocytopenia are seen, and therapy is started. Transfusion is contraindicated in thrombotic TTP, as it fuels the coagulopathy. Since the early 1990s, plasmapheresis has become the treatment of choice for TTP. This is an exchange transfusion involving removal of the patient's blood plasma through apheresis and replacement with donor plasma (fresh frozen plasma or cryosupernatant); the procedure must be repeated daily to eliminate the inhibitor and abate the symptoms. If apheresis is not available, fresh frozen plasma can be infused, but the volume that can be given safely is limited due to the danger of fluid overload. Plasma infusion alone is not as beneficial as plasma exchange. Corticosteroids (prednisone or prednisolone) are usually given. Rituximab, a monoclonal antibody aimed at the CD20 molecule on B lymphocytes, may be used on diagnosis; this is thought to kill the B cells and thereby reduce the production of the inhibitor. A stronger recommendation for rituximab exists where TTP does not respond to corticosteroids and plasmapheresis.

Caplacizumab is an alternative option in treating TTP as it has been shown that it induces a faster disease resolution compared with those patient who were on placebo. However, the use of caplacizumab was associated with increase bleeding tendencies in the studied subjects.

Most patients with refractory or relapsing TTP receive additional immunosuppressive therapy, e.g. vincristine, cyclophosphamide, splenectomy or a combination of the above.

Children with Upshaw-Schülman syndrome receive prophylactic plasma every two to three weeks; this maintains adequate levels of functioning ADAMTS13. Some tolerate longer intervals between plasma infusions. Additional plasma infusions may necessary for triggering events, such as surgery; alternatively, the platelet count may be monitored closely around these events with plasma being administered if the count drops.

Measurements of blood levels of lactate dehydrogenase, platelets, and schistocytes are used to monitor disease progression or remission. ADAMTS13 activity and inhibitor levels may be measured during follow-up, but in those without symptoms the use of rituximab is not recommended.

Anti-platelet autoantibodies in a pregnant woman with ITP will attack the patient's own platelets and will also cross the placenta and react against fetal platelets. Therefore, ITP is a significant cause of fetal and neonatal immune thrombocytopenia. Approximately 10% of newborns affected by ITP will have platelet counts <50,000/uL and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with neonatal alloimmune thrombocytopenia (NAIT).

No lab test can reliably predict if neonatal thrombocytopenia will occur. The risk of neonatal thrombocytopenia is increased with:

- Mothers with a history of splenectomy for ITP

- Mothers who had a previous infant affected with ITP

- Gestational (maternal) platelet count less than 100,000/uL

It is recommended that pregnant women with thrombocytopenia or a previous diagnosis of ITP should be tested for serum antiplatelet antibodies. A woman with symptomatic thrombocytopenia and an identifiable antiplatelet antibody should be started on therapy for their ITP which may include steroids or IVIG. Fetal blood analysis to determine the platelet count is not generally performed as ITP-induced thrombocytopenia in the fetus is generally less severe than NAIT. Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia. It is recommended that neonates be followed with serial platelet counts for the first few days after birth.,

Blood relatives of the proband case should be evaluated for the presence of hypodysfibrinogenemia. Individuals with the disorder need to be advised on its inheritance, complications, and preventative measures that can be taken to avoid bleeding and/or thrombosis. Since >80% of individuals may develop bleeding or thrombosis complications of the disorder, asymptomatic individuals diagnosed with hydposyfibrinogenemia are best handled at a specialized center in order to benefit from multidisciplinary management.

Measures to prevent and/or treat complications of hypodysfibrinogenemia should be tailored to the personal and family history of the individual by a specialized center. Individuals with a personal or family history of bleeding are considered to be of low risk of bleeding when their functional fibrinogen levels are >1 gram/liter for major surgery, >0.5 gram/liter for minor surgery, >0.5 to 1-2 gram/liter for spontaneous bleeding (depending on its severity), >0.5 to > 1 gram/liter for the first two trimesters of pregnancy, and >1 to <2 gram/liter for the last trimester of pregnancy and postpartum period. Functional fibrinogen below these levels should be treated preferably with fibrinogen concentrate or if not available, fibrinogen-rich cryoprecipitate or plasma to attain low risk levels of functional fibrinogen. Antifibrinolytic drugs such as tranexamic acid or (ε-aminocaproic acid) may be considered as an alternative preventative or therapeutic treatments in cases of minor surgery, dental extractions, mucosal bleeding, or other episodes of mild bleeding. In individuals with a personal or family history of thrombosis, should be considered for long-term anticoagulation drugs such as low molecular weight heparin, coumadin, or rivaroxaban.

The mortality rate is around 95% for untreated cases, but the prognosis is reasonably favorable (80–90% survival) for patients with idiopathic TTP diagnosed and treated early with plasmapheresis.

Giant platelet disorders are rare disorders featuring abnormally large platelets, thrombocytopenia and a tendency to bleeding. Giant platelets cannot stick adequately to an injured blood vessel walls, resulting in abnormal bleeding when injured. Giant platelet disorder occurs for inherited diseases like Bernard-Soulier syndrome, gray platelet syndrome and May-Hegglin anomaly.

Individuals with hypofibrinogenemia who have a history of excessive bleeding should be treated at a center specialized in treating hemophilia and avoid all medications that interfere with normal platelet function. During bleeding episodes, treatment with fibrinogen concentrates or, if unavailable infusion of fresh frozen plasma and/or cryoprecipitate (a fibrinogen-rich plasma fraction) to maintain fibrinogen activity levels >1 gram/liter.

Individuals with hypofibrinogenemia who experience episodic thrombosis should also be treated at a center specialized in treating hemophilia. Standard recommendations for these individuals are that they use antithrombotic agents and be instructed on antithrombotic behavioral methods in high risk situations (e.g. long car rides and air flights]]. Acute venous thrombosis episodes should be treated with low molecular weight heparin for a time that depends on personal and family history of thrombosis events. Prophylactic treatment prior to minor surgery should avoid fibrinogen supplementation and use anticoagulation measures; prior to major surgery, fibrinogen supplementation should be used only if serious bleeding occurs; otherwise, prophylactic anticoagulation measures are recommended.

Not all those affected will require treatment at presentation. People are usually split up into low and high risk for bleeding/blood clotting groups (based on their age, their medical history, their blood counts and their lifestyles), low risk individuals are usually treated with aspirin, whereas those at high risk are given hydroxycarbamide and/or other treatments that reduce platelet count (such as interferon-α and anagrelide).

In 2007, the drug eculizumab was approved for the treatment of PNH. It improves quality of life and decreases the need for blood transfusions but does not appear to affect the risk of death. It does not appear to change the risk of blood clots, myelodysplastic syndrome, acute myelogenous leukemia, or aplastic anemia.

Eculizumab is controversial due to its high cost, as it is among the most expensive pharmaceuticals in the world, with a price of US$440,000 per person per year. Eculizumab is a humanized monoclonal antibody that acts as a terminal complement inhibitor. The U.S. Food and Drug Administration (FDA) has issued a black-box warning for eculizumab whose recipients have a 1,000 to 2,000-fold greater risk of invasive meningococcal disease compared to the general U.S. population. Patients for whom eculizumab is prescribed are strongly advised by the FDA to receive meningococcal vaccination at least two weeks prior to starting therapy and to consider antimicrobial prophylaxis for the duration of treatment with eculizumab.