Approach to bleeding disorder (coagulation defects) in children
Dr. Vadapalli SATISH SMIMS, GangtokMD Paeds. 2nd year
A bleeding tendency is a presentation with bleeding in a patient in whom no anatomical cause for the bleeding (i.e., trauma to a vessel for one of many possible reasons) can be discovered. It is then inferred that the bleeding is due to a functional impairment of the normal hemostatic process.
This impairment may be due to1. A functional deficiency in the procoagulantmechanism. This may involvea. The plateletsb. The procoagulant plasma components
2. A functional excess in anticoagulantmechanisms.a. Anticoagulant drugsb. Natural anticoagulants3. A functional excess in the fibrinolyticmechanism.
Broadly we can identify three types: „„COAGULATION-DEFECT BLEEDS,‟‟ „„PURPURIC-TYPE BLEEDS,‟‟ and MIXED bleeds.
Localized cyanosis is differentiated from ecchymosis by the momentary blanching pallor (with cyanosis) occurs after pressure
Finding Disorders of Disorders of Coagulation Platelets or VesselsPetechiae Rare CharacteristicDeep dissecting Characteristic RarehematomasSuperficial Common; usually Characteristic;ecchymoses large and usually small and solitary multipleHemarthrosis Characteristic RareDelayed bleeding Common RareBleeding from Minimal Persistent often profusesuperficial cuts andscratchesSex of patient 80–90% of inherited Relatively more forms occur only in common in females male patientsPositive family Common Rare (exc. vWF ,history hereditary hemorr. telangiectasia)
Major Types Disorders ExamplesAcquired Acquired Neutralizing antibodies against factors V, VIII, antibodies and XIII, accelerated clearance of antibody- against factor complexes, e.g., acquired von coagulation Willebrand disease, hypoprothrombinemia factors associated with antiphospholipid antibodies DIC Acute (sepsis, malignancies, trauma, obstetric complications) and chronic (malignancies, giant hemangiomas, retained products of conception) Drugs Antiplatelet agents, anticoagulants, antithrombins, and thrombolytic, hepatotoxic, and nephrotoxic agents Vascular Nonpalpable purpura ("senile," solar, and factitious purpura), use of corticosteroids, vitamin C deficiency, child abuse, thromboembolic, purpura fulminans; palpable- purpura (Henoch-Schönlein, vasculitis, dysproteinemias; amyloidosis
Table 118–1. Classification of Disorders of HemostasisMajor Types Disorders ExamplesInherited Deficiencies of Hemophilia A (factor VIII deficiency), coagulation hemophilia B (factor IX deficiency), factors deficiencies of fibrinogen factors II, V, VII, X, XI, and XIII and von Willebrand disease Platelet Glanzmann thrombasthenia, Bernard- disorders Soulier syndrome, platelet granule disorders Fibrinolytic 2-Antiplasmin deficiency, plasminogen disorders activator inhibitor-1 deficiency Vascular Hemorrhagic telangiectasias Connective Ehlers-Danlos syndrome tissue disorders
1.Patients vary in their responses to hemorrhagic symptoms. Therefore, some experts believe the question "Do you bruise easily?" is virtually worthless. Women more likely respond that they have excessive bleeding or bruising than do men.
2. Unprovoked hemarthroses and muscle hemorrhages suggest one of the hemophilias. mucocutaneous bleeding (epistaxis, gingival bleeding, menorrhagia) are more characteristic of patients with qualitative platelet disorders, thrombocytopenia, or von Willebrand disease.
3. Assessing the extent of hemorrhage against the background of any trauma or provocation that may have elicited the hemorrhage is important. If a patient has never had a significant hemostatic challenge (such as tooth extraction, surgery, trauma, or childbirth), the lack of a significant bleeding history is much less valuable in excluding a mild hemorrhagic disorder.
4. Obtaining objective confirmation of the subjective information conveyed in the bleeding history is valuable. Objective data include (a) previous hospital or physician visits for bleeding symptoms, (b) results of previous laboratory evaluations, (c) previous transfusions of blood products for bleeding episodes, and (d) a history of anemia and/or previous treatment with iron.
5. A medication history esp. non-prescription drugs. A medication history is especially important in patients with thrombocytopenia, because drug-induced thrombocytopenia is common. Medication also may affect hemostasis through deleterious effects on the liver or kidney functions.
Herbal and alternative medicines poses particular problems, because patients may not readily share information about the drug and the dose they are taking of any particular active ingredient may be difficult to determine. Ginkgo biloba and ginseng are the most commonly used herbals that can cause platelet dysfunction and induce bleeding. Other dietary supplements.
6. A nutrition history should be obtained to assess the likelihood of (a) vitamin K deficiency, especially if the patient also is taking broad-spectrum antibiotics, (b) vitamin C deficiency, especially if the patient has skin bleeding consistent with scurvy (perifollicular purpura), and (c) general malnutrition and/or malabsorption.
7. Several tissues have an increased local fibrinolytic activity. urinary tract, endometrium, and mucous membranes of the nose and oral cavity. These sites are particularly likely to have prolonged oozing of blood after trauma in patients with hemostatic abnormalities. Excessive bleeding following tooth extraction is one of the most common manifestations.
8.Bleeding isolated to a single organ or system (e.g., hematuria, hematemesis, melena, hemoptysis) is less likely to result from a hemostatic abnormality than from a local cause such as neoplasm, ulcer, or angiodysplasia. Thus, careful anatomic evaluation of the involved organ or system should be performed.
9.Bleeding may result from blood vessel disorders such as hereditary hemorrhagic telangiectasias, Cushing disease, scurvy, or Ehlers-Danlos syndrome. Many primary dermatologic disorders also have a purpuric or hemorrhagic component and must also be considered in the differential diagnosis.
10. A family history is particularly important when hereditary disorders are considered. consanguinity, genealogic tree, extending back at least two generations for genetic disorders. A sex-linked pattern hemophilia A or B An AD, most forms of vWD An AR, coagulation factor deficiencies, inherited platelet disorders, and the rare, severe, type 3 von Willebrand disease.
11.Population genetic information may be helpful; for example, the higher prevalence of factor XI deficiency in Ashkenazi Jews
12.Diseases and organs that may affect hemostasis, such as cirrhosis, renal insufficiency, myeloproliferative disorders (e.g., essential thrombocythemia), acute leukemia, myelodysplasia, systemic lupus erythematosus, and Gaucher disease.
Table 118–2. Clinical Manifestations Typically Associated withSpecific Hemostatic DisordersClinical Manifestations Hemostatic DisordersMucocutaneous bleeding Thrombocytopenias, platelet dysfunction, von Willebrand diseaseCephalhematomas in Severe hemophilias A and B, severenewborns, hemarthroses, deficiencies of factor VII, X, or XIII,hematuria, and intramuscular, severe type 3 von Willebrand disease,intracerebral, and afibrinogenemiaretroperitoneal hemorrhagesInjury-related bleeding and Mild and moderate hemophilias A and B,mild spontaneous bleeding severe factor XI deficiency, moderate deficiencies of fibrinogen and factors II, V, VII, or X, combined factors V and VIII deficiency, 2-antiplasmin deficiency
Table 118–2. Clinical Manifestations Typically Associated withSpecific Hemostatic DisordersBleeding from stump of Afibrinogenemia, hypofibrinogenemia,umbilical cord and habitual dysfibrinogenemia, factor XIII deficiencyabortionsImpaired wound healing Factor XIII deficiencyFacial purpura in newborns Glanzmann thrombasthenia, severe thrombocytopeniaRecurrent severe epistaxis Hereditary hemorrhagic telangiectasiasand chronic iron deficiencyanemia
1. Epistaxis is one of the most common symptoms of platelet disorders & vWD. It also is the most common symptom of hereditary hemorrhagic telangiectasia. epistaxis - more severe with advancing age. Epistaxis is not uncommon in normal children, usu. resolves before puberty. Dry air heating systems can provoke epistaxis even in normal individuals. Bleeding confined to a single nostril - local vascular problem than a systemic coagulopathy.
2. Gingival hemorrhage is very common in patients with both qualitative and quantitative platelet abnormalities and von Willebrand disease. Occasional gum bleeding occurs in normal. 3. Oral mucous membrane bleeding in the form of blood blisters is a common manifestation of severe thrombocytopenia. Such bleeding usually has a predilection for sites where teeth can traumatize the inner surface of the cheek.
4. Skin hemorrhage in the form of petechiae and ecchymoses are common manifestations of hemostatic & non-hemostatic disorders. Excessive bruising is more common in women than men. Bruising varies with the phase of their menstrual cycle. Severity of skin hemorrhage include the size, the frequency, spontaneously or only with trauma, and bruises on non traumatized regions, such as the trunk and back.
5. The color of the bruise Red bruises on the extensor surfaces of the arms and hands indicate loss of supporting tissues, as occurs in Cushing syndrome, glucocorticoid therapy, senile purpura, and damage from chronic sun exposure. Jet-black bruises-warfarin induced skin necrosis.
Easybruising can also occur in patients with Ehlers-Danlos syndrome manifested by distensible skin or extraordinary ligament laxness, and in patients with hyperflexibility of the thumb.
6.Tooth extractions - helpful in defining the risk of bleeding. Molar extractions >> extractions of other teeth. Objective data regarding excessive bleeding based on the need for blood products or the need to pack or suture the extraction site are valuable. 7. Excessive bleeding in response to razor nicks is common in patients with platelet disorders or von Willebrand disease.
8. Hemoptysis- never a bleeding disorder and is rare even in patients with serious bleeding disorders. However, blood-tinged sputum in association with upper respiratory tract infections may be more common in patients with hemostatic disorders.
9. Hematemesis- never a hemostatic disorder. However, a hemostatic disorder may lead to hematemesis because of an anatomic abnormality in the upper gastrointestinal tract. Some hemostatic disorders more likely result in hematemesis because of a combination of effects, such as liver disease with deficient synthesis of coagulation proteins and with esophageal varices and aspirin ingestion with gastritis.
10. Hematuria-rarely presenting c/o -exc. for the hemophilias. However, hemostatic disorders-exacerbate hematuria caused by other disorders,eg. UTI. 11. Rectal bleeding-in normal-hemorrhoids. von Willebrand disease and platelet disorders - associated with a number of different underlying causes, including diverticuli, hemorrhoids, or angiodysplasia. Melena-rarely the presenting symptom. But, repeated episodes-hemor. disorders.
12. Menorrhagia is common in women with platelet disorders and von Willebrand disease. In general, menstrual bleeding is considered excessive if the patient indicates she has heavy flow for more than 3 days or total flow for more than 7 days. objective distinction b/w menorrhagia (loss of more than 80 mL blood per period) and normal blood loss can only be made by a visual assessment technique using pictorial charts of towels or tampons.
13. Postpartum hemorrhage- bleeding disorders commonly manifest excessive bleeding during or after labor necessitating blood transfusion. 14. Habitual spontaneous abortions raise the possibility that the patient has a quantitative or qualitative abnormality of fibrinogen, factor XIII deficiency, or the antiphospholipid syndrome.
15.Hemarthroses are the hallmark abnormality in the hemophiliac; severe factor VII deficiency and type 3 von Willebrand disease patients may not recognize that their symptoms (pain, swelling, and limitation of motion) are caused by bleeding into their joints.
16.Excessive hemorrhage associated with surgical procedures is common in patients with hemorrhagic disorders. Procedures involving tissues with increased local fibrinolytic activity like urinary tract, nose, tonsils and oral cavity are particularly prone to bleed.
17. Excessive bleeding following circumcision is common in males with severe hemostatic disorders such as hemophilia A, hemophilia B, or Glanzmann thromboasthenia, and often is the patients first symptom. 18. Bleeding from the umbilical stump is characteristic of factor XIII deficiency and afibrinogenemia.
PT measures – THE EXTRINSIC PATHWAY PT is prolonged with deficiencies of factors VII, V, X, II, I. In most laboratories, the normal PT value is 10-13 sec. PT has been standardized using the International Normalized Ratio (INR) so that values can be compared from 1 laboratory or instrument to another. This ratio is used to determine similar degrees of anticoagulation with warfarin (Coumadin)– like medications.
This test measures the – INTRINSIC PATHWAY- initiation of clotting at the level of factor XII through sequential steps to the final clot end-point. In vivo, activation of factor XII, by prekallikrein and HMWK. In lab, factor XII is activated using a surface (silica or glass) or a contact activator, such as ellagic acid.
Factor XIIa => factor XI - XIa, => factor IX to factor IXa. On the platelet phospholipid surface, factor IXa complexes with factor VIII and calcium to activate factor X (“tenase”complex). accelerated by interaction with phospholipid and calcium, involving factors V and VIII.
An isolated deficiency of a single clotting factor may result in isolated prolongation of PT, PTT, or both, depending on the location of the factor in the clotting cascade. This approach is useful in determining hereditary clotting factor deficiencies; however, in acquired hemostatic disorders encountered in clinical practice, > 1 clotting factor is frequently deficient, so the relative prolongation of PT and PTT must be assessed.
Normal ranges for PTT are much more variable from laboratory to laboratory than those for PT. Thus, the mechanisms studied by PT and PTT allow the evaluation of clotting factor deficiencies, even though these pathways may not be the same as those occurring physiologically.
In vivo, factor VIIa activates factors IX and X, Lab.- factor VIIa => factor X only. This explain why the most severe bleeding disorders are hemophilias factor VIII & IX. In vivo, II feeds back to XI and accelerate the clotting process. PTT can be prolonged by deficiencies of factor XII, prekallikrein, and HMWK, yet NO BLEEDING.
Ifprolong. PT, PTT, or TT=> a mixing study. Normal plasma is added to the patients plasma, and the PT or PTT is repeated. Correction of PT or PTT => def. of a clotting factor, (because a 50% level of individual clotting proteins is sufficient to produce normal PT or PTT.)
Ifthe clotting time is not corrected or only partially corrected, an inhibitor is usually present. An inhibitor of clotting may be - -either a chemical similar to heparin that delays coagulation -or an antibody directed against a specific clotting factor.(MC- VIII, IX, or XI, may be present). -or the phospholipid used in clotting tests.
In the inpatient setting, the most common cause of this finding is heparin contamination of the sample. The presence of heparin in the sample can be ruled in or out with the use of thrombin time and reptilase time. Ifno bleeding and both PTT and the mixing study are prolonged, a lupus-like anticoagulant is often present.(clinical predisposition to excessive clotting)
Prolongation of thrombin time occurs in--reduced fibrinogen levels(hypofibrinogenemia or afibrinogenemia).-dysfunctional fibrinogen(dysfibrinogenemia), or-the use of substances that interfere withfibrin polymerization, such as heparin orfibrin split products.
TT measures the final step in the clotting cascade, (fibrinogen => fibrin). The normal TT is usu. 11–15 sec. In heparin contamination, RT is usually ordered.
RT uses snake venom to clot fibrinogen. Unlike TT, RT is not sensitive to heparin RT is inc. only by reduced or dysfunctional fibrinogen and fibrin split products. If TT is inc and RT is N = Heparin (not reduced concentration or function of fibrinogen)
Bleeding time assesses the function of platelets and their interaction with the vascular wall. Disposable standardized devices have been developed that control the length and depth of the skin incision. A blood pressure cuff is applied to the upper arm and inflated to 40 mm Hg for children and adults. In term newborns and younger children, a modified device has been developed that is used with a lower blood pressure cuff pressure.
After an incision is made with the bleeding time device, blood is blotted from the margin of the incision at 30-sec intervals until bleeding ceases. usually stops within 4-8 min. Bleeding time is a difficult laboratory test to standardize, and there is much interlaboratory and interindividual variation. prolonged bleeding time, qualitative platelet defect or VWD, PLC< 1 lakh/cu.mm
Essentials of Diagnosis & Typical Features -Easy bruising and epistaxis from early childhood. -Menorrhagia. -Prolonged PFA-100 (or bleeding time); normal platelet count; absence of acquired platelet dysfunction. -Reduced activity or abnormal structure of vWF.
the most common inherited bleeding disorder among Caucasians, with a prevalence of 1%. vWF is a protein present as a multimeric complex in plasma, which binds factor VIII and is a cofactor for platelet adhesion to the endothelium. An estimated 70–80% - classic vWD (type 1) - partial quantitative deficiency of vWF. vWD type 2 involves a qualitative deficiency of (ie, dysfunctional) vWF, and vWD type 3 - nearly complete deficiency of vWF.
The majority (> 80%) with type 1 disease are asymptomatic. vWD is most often transmitted as AD trait, but can be AR. The disease can also be acquired, developing in association with hypothyroidism, Wilms tumor, cardiac disease, renal disease, or systemic lupus erythematosus and in individuals receiving valproic acid. Acquired vWD is most often caused by the development of an antibody to vWF or increased turnover of vWF.
A history of increased bruising and excessive epistaxis is often present. Prolonged bleeding also occurs with trauma or at surgery. Menorrhagia is often a presenting finding in females.
PT is normal, and aPTT is sometimes prolonged. Prolongation of the PFA-100 or bleeding time is usually present since vWF plays a role in platelet adherence to endothelium. Dec PLC in type 2b vWD. Factor VIII and vWF antigen are decreased in types 1 and 3, but may be normal in type 2 vWD. vWF activity (eg, ristocetin cofactor or collagen binding) is decreased in all types. BGT important - normal vWF antigen levels.( O has least levels) vWF multimer assay- complete classification
The treatment to prevent or halt bleeding for most patients with vWD types 1 and 2 is desmopressin acetate, release of vWF from endothelial stores. Desmopressin may IV / Intranasal. Because response to vWF is variable among patients, factor VIII and vWF activities are typically measured before and 60 minutes after infusion.
Desmopressin may cause fluid shifts, hyponatremia, and seizures in children younger than 2 years of age. Tachyphylaxis- limited stores. vWF-replacement therapy (eg, plasma- derived concentrate) is recommended; Antifibrinolytic agents (eg, -aminocaproic acid) , Topical thrombin and fibrin glue may be useful for control of mucosal bleeding. Estrogen-OCP-for menorrhagia.
desmopressin via release of endothelial stores of factor VIII and vWF into plasma exogenous factor VIII. The in-vivo half-life of factor VIII is generally 8–12 hours. Non–life-threatening, non–limb-threatening hemorrhage is treated initially with 20–30 U/kg of factor VIII- rise in plasma factor VIII activity to 40–60%. Large joint hemarthrosis and life- or limb- threatening hemorrhage is - 50 U/kg. Prophylactic factor VIII infusions (eg, two or three times weekly)
Withthe availability of effective treatment and prophylaxis for bleeding, life expectancy in vWD is normal.
Comparison of vWD and Hemophilias Hemophilia A Hemophilia B von Willebrand DiseaseFactor VIII Low Normal Low or normalcoagulantactivityvon Willebrand Normal Normal Lowfactor antigenvon Willebrand Normal Normal Lowfactor activityFactor IX Normal Low NormalRistocetin- Normal Normal Normal, low, or increasedinduced platelet at low-dose ristocetinagglutinationPlatelet Normal Normal NormalaggregationTreatment DDAVP* or Recombinant IX recombinant VIII
Essentials of Diagnosis & Typical Features Bruising, soft-tissue bleeding, hemarthrosis. Prolonged activated partial thromboplastin time (aPTT). Reduced factor VIII activity.
General Considerations Factor VIII activity is reported in units per milliliter, with 1 U/mL equal to 100% of the factor activity found in 1 mL of normal plasma. The normal range for factor VIII activity is 0.5–1.5 U/mL (50–150%). Hemophilia A occurs predominantly in males as an X- linked disorder. One third of cases are due to a new mutation. The incidence of factor VIII deficiency is 1:5000 male births.
severe hemophilia A (< 1% plasma factor VIII activity) spontaneous bleeding episodes involving skin, mucous membranes, joints, muscles, and viscera. Those with moderate hemophilia A (1% to < 5% factor VIII activity) typically have intermediate bleeding manifestations mild hemophilia A (5–40% factor VIII activity) bleed only at times of trauma or surgery. recurrent hemarthroses that incite joint destruction.
prolonged aPTT, (PT) is normal. Diagnostic- decreased factor VIII activity with normal vWF activity. In 2/3rds of families of hemophilic patients, the females are carriers and some are mildly symptomatic. Carriers of hemophilia can be detected by determination of the ratio of factor VIII activity to vWF antigen and by molecular genetic techniques. In a male fetus or newborn with a family history of hemophilia A, cord blood sampling for factor VIII activity is accurate and important in subsequent care.
Intracranial hemorrhage. Hemarthroses begin early in childhood- joint destruction (ie, hemophilic arthropathy). Large intramuscular hematomas - compartment syndrome with resultant muscle and nerve death. A serious complication - acquired circulating antibody to factor VIII after treatment with factor VIII concentrate. 15–25% of patients with severe hemophilia A, - desensitization - immunosuppressive therapy recombinant factor VIIa has become a therapy of choice.
infection with the human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Inactivation methods do not eradicate viruses lacking a lipid envelope, however, so that transmission of parvovirus and hepatitis A remains a concern with the use of plasma- derived products. Immunization with hepatitis A and hepatitis B vaccines is recommended for all hemophilia patients
Factor XI deficiency is an AD, with mild to moderate bleeding symptoms. It is frequently encountered in Ashkenazi Jews but has been found in many other ethnic groups. In Israel,1-3/1,000 individuals are homozygous for this deficiency. The bleeding tendency is not as severe and not correlated with the amount of factor XI. Some patients with severe deficiency may have minimal or no symptoms at the time of major surgery.
Because factor XI => + thrombin => + fibrinolytic inhibitor TAFI , surgical bleeding is more prominent in sites of high fibrinolytic activity like the oral cavity. Unless the patient previously had surgery without bleeding, replacement therapy should be considered and given preoperatively, depending on the nature of the surgical procedure. No approved concentrate of factor XI is available in the USA; therefore, the physician must use fresh frozen plasma (FFP).
Bleeding during minor surgery can be controlled with local pressure. Patients undergoing dental extractions can be monitored closely and may benefit from treatment with fibrinolytic inhibitors like aminocaproic acid, with plasma replacement therapy used only if hemorrhage occurs. In a patient with homozygous deficiency of factor XI, PTT is often longer than it is in patients with either severe factor VIII or factor IX deficiency. Chronic joint bleeding is rarely a problem in factor XI deficiency, and for most patients, the deficiency is a concern only at the time of major surgery unless there is a second underlying hemostatic defect (e.g.,von Willebrand disease)
The paradox of fewer clinical symptoms in combination with longer PTT is surprising, but it occurs because factor VIIa can activate factor IX in vivo. Diagnostic- specific factor XI assays. Plasma infusions of 1 IU/kg usually increase the plasma concentration by 2%. Thus, infusion of plasma at 10-15 mL/kg will result in a plasma level of 20-30%,which is usually sufficient to control moderate hemorrhage. half-life of factor XI is usually ≥48 hr,
Deficiency of the “contact factors” (factor XII, prekallikrein, and high molecular weight kininogen) causes prolonged PTT but no bleeding symptoms. the paradoxical situation in which PTT is extremely prolonged with no evidence of clinical bleeding. they do not need treatment, even for major surgery.
Factor VII deficiency is a rare autosomal bleeding disorder- detected only in homozygous. Severity of bleeding varies from mild to severe with hemarthroses, spontaneous intracranial hemorrhage, and mucocutaneous bleeding, especially nosebleeds and menorrhagia. markedly prolonged PT,normal PTT,& dec Factor VII assays. Because the plasma half-life of factor VII is 2-4 hr, therapy with FFP is difficult and is often complicated by fluid overload. A commercial concentrate of recombinant factor - not approved by the FDA yet.
Factor X deficiency is a rare (estimated 1/1,000,000) autosomal disorder with variable severity. Mild deficiency -mucocutaneous and post- traumatic bleeding, severe deficiency - hemarthroses and intracranial hemorrhages. Factor X deficiency is the result of either a quantitative deficiency or a dysfunctional molecule. prolongation of both PT and PTT.
Rx-FFP or prothrombin complex concentrate. The half-life of factor X is approximately 30 hr, and its volume of distribution is similar to that of factor IX. Thus, 1 U/kg will increase the plasma level of factor X by 1%. rarely, systemic amyloidosis-X deficiency, adsorption of factor X on amyloid protein. transfusion therapy often is not successful because of the rapid clearance of factor X.
By reduced prothrombin level (hypoprothrombinemia) , or by functionally abnormal prothrombin (dysprothrombinemia). Laboratory testing in homozygous patients shows prolonged PT and PTT. Factor II, or prothrombin, assays show a markedly reduced prothrombin level. Mucocutaneous bleeding in infancy and post-traumatic bleeding later are common.
Rx- FFP or, rarely, prothrombin complex concentrates. FFP is useful, because the half-life of prothrombin is 3.5 days. Administration of 1 IU/kg of prothrombin will increase the plasma activity by 1%.
autosomal recessive, mild to moderate bleeding disorder that has also been termed parahemophilia. mucocutaneous bleeding and hematomas MC symptoms. Severe menorrhagia is a frequent symptom in women. Hemarthroses occur rarely. Lab- prolonged PTT and PT. Specific assays for factor V show a reduction. FFP is only option. V is lost rapidly from stored FFP.
Patients with severe factor V deficiency are treated with infusions of FFP at 10 mL/kg every 12 hr. Rarely, acquired antibody to factor V . Such pt. does not bleed because the factor V in platelets prevents excessive bleeding.
secondary to the absence of an intracellular transport protein that is responsible for transporting factors V and VIII from the endoplasmic reticulum to the Golgi compartments. paradoxical deficiency of 2 factors, one encoded on chromosome 1and X chromosome. Bleeding symptoms are often milder than for hemophilia A . Rx- FFP to replace both factors V and VIII.
rare autosomal recessive disorder in which there is an absence of fibrinogen. do not bleed as frequently as hemophiliacs, rarely have hemarthroses. neonatal period with GI hemorrhage or hematomas after vaginal delivery. marked prolongation of PT and PTT, thrombin time . an unmeasurable fibrinogen level is diagnostic.
dysfunctional fibrinogens have been reported (dysfibrinogenemia). present with thrombosis. half-life of fibrinogen is 2-4 days, treatment with either FFP or cryoprecipitate is effective. Fibrinogen are inhibited by high doses of heparin. Prolonged reptilase time confirms that functional levels of fibrinogen are low and that heparin is not present.
Because factor XIII is responsible for the cross linking of fibrin to stabilize the fibrin clot, symptoms of delayed hemorrhage are secondary to instability of the clot. Typically, patients have trauma 1 day and then have a bruise or hematoma the next day. Clinical symptoms include mild bruising, delayed separation of the umbilical stump beyond 4 wk in neonates, poor wound healing, and recurrent spontaneous abortions Rare hemarthroses and intracranial hemorrhage have been described.
PT, PTT, TT, BT are Normal there is increased solubility of the clot because of the failure of cross linking. The normal clot remains insoluble in the presence of 5M urea, whereas in a patient with XIII deficiency, the clot dissolves. More specific assays for factor XIII a. half-life of factor XIII is 5-7 days and the hemostatic level is 2-3% activity, infusion of FFP or cryoprecipitate will correct the deficiency.
Deficiency of either antiplasmin or plasminogen activator inhibitor, both of which are antifibrinolytic proteins=> increased plasmin => premature lysis of fibrin clots. mild bleeding disorder, mucocutaneous bleeding but rarely have joint hemorrhages. usual hemostatic tests are normal+ positive bleeding history => euglobulin clot lysis time, which measures fibrinolytic activity = shortened result.
Specificassays for α2-antiplasmin and plasminogen activator inhibitor are available. Bleeding episodes are treated with FFP; bleeding in the oral cavity may respond to aminocaproic acid
The clinical phenotype of severe protein C deficiency in neonatal purpura fulminans implies that APC exerts multiple physiologically essential activities, including potent anticoagulant and anti-inflammatory actions . Recent advances establish that APCs antiinflammatory actions are but one manifestation of its ability to interact directly with cell receptors to provide multiple cytoprotective activities. These two distinct types of activities of APC, intravascular anticoagulant activity and initiation of cell signaling, are mediated by different sets of molecular interactions, and both types of activities are clinically relevant.
Component Content Indication Dose Outcome expectdFresh frozen 1unit/mL Multiple clotting 10-15 mL/kg Improvement inplasma of each factor deficiency prothrombin and clotting partial factor thromboplastin timesCryoprecipit Fibrinoge Hypofibrinogene 1 bag/5 kg ↑ Fibrinogen byate n, factor mia, factor XIII 50-100 mg/dL VIII, vWF, deficiency factor XIIIRecombinant Units as Hemophilic F VIII: 20-50 FVIII: 2%/unit/kgfactor labeled bleeding or units/kg* FIX: 0.7/unit/kgconcentrates prophylaxis F IX: 40-120 units/kg*Recombinant μg Hemophilic 90 μg/kg q3 h Cessation offactor VIIa bleeding in bleeding(NovoSeven) inhibitor patient; uncontrolled post operative hemorrhage
Comparison of vWD and Hemophilias Hemophilia A Hemophilia B von Willebrand DiseaseInheritance X-linked X-linked Autosomal dominantFactor deficiency Factor VIII Factor IX von Willebrand factor and VIIICBleeding site(s) Muscle, joint, Muscle, joint, Mucous membranes, skin, surgical surgical surgical, menstrualProthrombin time Normal Normal NormalActivated partial Prolonged Prolonged Prolonged or normalthromboplastintimeBleeding time Normal Normal Prolonged or normal
1. In hematology – we cant do without blood test.2. Only Blood test are not enough.
A 15-year-old boy with chronic strep throat has presented with excessive bruising. His coagulation results were as follows: PT 15.5 seconds (Reference range, 10.8 to 13.5) aPTT 42.1 seconds (Reference range, 28.5 to 35.5) Platelets 325,000 (Reference range, 150,000 to 400,000) Bleeding 5 minutes (Reference, 8 minutes) Which coagulation tests are abnormal, and how should this physician proceed in his treatment of this patient?
In this case, two parameters, the PT and aPTT, are elevated. The patient is not bleeding, but he shows a history of recent bruising. Since both the PT and the aPTT are affected, one can assume the problem is in the common pathway, speciﬁcally factors I, II, V, and X. Factor assays could be performed to assess the level of activity of each of these clotting factors; however, a closer examination into the patient‟s history might reveal an additional feature. Since this patient has had chronic strep throat, it is logical to assume that he has been on long-term antibiotics.
Antibioticsmay deplete the normal ﬂora, a source of vitamin K synthesis. Factors II, VII, IX, and X are vitamin K–dependent factors. Vitamin K is the essential cofactor for the gamma carboxyglutamic acid residues necessary to activate these factors. When vitamin K is in short supply or depleted, these factors fail to function properly. In our patient, vitamin K can be given by mouth to resume normal coagulation and correct bruising.