Bleeding diathesis
Bleeding diathesis main page |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Mehrian Jafarizade, M.D [2], Nazia Fuad M.D.
Overview
Bleeding diathesis is unusual susceptibility to bleed due to hypo-coagulopathies. These diseases can occur due to a disorder of homeostasis, localized process (tissue injury), or medications. Bleeding diathesis can be resulted from vessel wall injury, platelet disorders, and coagulation factor disorders. Clinical manifestation of bleeding disorders can have a wide range of symptoms from asymptomatic to symptomatic massive and life threatening bleeding. Platelet disorders mostly have skin manifestations such as petechiae, and ecchymoses. In order to find the cause of hypo-coagulopathy; there are established laboratory tests, such as peripheral blood smear, platelet count and platelet function analysis, coagulation factor deficiencies and inhibitors, fibrinolysis tests (eg. D-dimer level), bleeding time, prothrombin time, activated partial thromboplastin time, thrombin time and reptilase time.
Homostasis
Hemostasis is the process of blood clot formation at the site of bleeding. This process has 4 main phases as below:
Platelet plug formation
At the site of vascular injury platelets are activated and bound to the collagen with the surface collagen-specific glycoprotein Ia/IIa receptor. This bindings are provided by the linking of large multimeric circulating protein von Willebrand factor (vWF). Ultimately, the platelets makes a platelet clot to initially stop the bleeding.
Coagulation cascade
Antithrombotic control
Fibrinolysis
For more information click here, and here.
Classification
Disorders of hemostasis can be classified into two main categories: platelet disorders, and disorders of coagulation. Each category can be further classified as bellow:
Platelet disorders:
- Thrombocytopenia: platelet count less than 150,000 per mm3
- Thromobcytosis: platelet countcmore than 450,000 per mm3
- Qualitative Disorders of Platelet function such as Von Willebrand Disease, inherited or acquired functional disorders.
Coagulation disorders
- Vessel wall disorders: Endothelial cells are lining entire vessel walls all over the body. Endothelium is an active layer responsible for inflammatory responses, angiogenesis and blood cell interactions. Endothelial cells have a very important role in hemostasis and they are regulating blood fluidity by the balance of antithrombotic/prothrombotic and vasodilatory/vasoconstrictor effects.
- Metabolic and Inflammatory Disorders
- Inherited Disorders of the Vessel Wall
- Coagulation factor disorders:
- Fibrinogen deficiency
- Prothrombin deficiency
- Factor V deficiency
- Factor VII deficiency
- Factor X deficiency
- Factor XII deficiency
- HK deficiency
- Prekallikrein deficiency
- Factor XIII deficiency
- Hemophilia
- Disseminated Intravascular Coagulation
- Vitamin K Deficiency
- Coagulation Disorders Associated with Liver Failure
- Acquired Inhibitors of Coagulation Factors
Differential Diagnosis
Category | Sub-category | Diseases | History | Clinical manifestation | Laboratory testing[1] | Comments | |||||||||
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Petechiae | Ecchymoses | Menorrhagia | Hematoma | Hemarthrosis | Platelet count | Bleeding time (BT) | Prothrombin time (PT) | Activated partial thromboplastin time (aPTT) | Thrombin time (TT) | ||||||
Platelet disorders | Thrombocytopenia | Infection-Induced thrombocytopenia |
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+ | + | + | + | + | ↓ | ↑ | N | N | N | - | |
Medications-Induced thrombocytopenia |
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+ | + | + | + | + | ↓ | ↑ | N | N | N | Most important par of treatment is discontinuing of the medication. | |||
Heparin-Induced thrombocytopenia |
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+ | + | + | + | + | ↓ | ↑ | N | N | ↑ | For more information click here: Heparin-induced thrombocytopenia. | |||
Immune Thrombocytopenic Purpura (ITP) |
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+ | + | + | + | + | ↓ | ↑ | N | N | N | - | |||
Inherited Thrombocytopenia |
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+ | + | + | + | + | ↓ | ↑ | N | N | N | - | |||
Thrombotic Thrombocytopenic Purpura (TTP) | History of:
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+ | + | + | + | + | ↓ | ↑ | N | N | N | - | |||
Hemolytic Uremic Syndrome | History of:
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+ | + | + | + | + | ↓ | ↑ | N | N | N | - | |||
Thromobcytosis |
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− | − | − | +/- | +/- | ↑ | Ν/↑ | ɴ | ɴ | N | - | |||
Qualitative Disorders of Platelet Function | Inherited Disorders of Platelet Function | Glanzmann’s thrombasthenia |
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+ | + | + | - | Rare | N/↓ | ↑ | ɴ | ɴ | N |
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Bernard-Soulier syndrome |
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+ | + | + | - | - | N/↓ | ↑ | N | N | N |
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Platelet storage pool disorder (SPD): |
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+ | + | + | - | - | N/↓ | ↑ | N | N | N |
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Acquired Disorders of Platelet Function |
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+ | + | + | +/- | +/- | N/↓ | ↑ | N | N | N | - | |||
Von Willebrand Disease [2][3] |
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+ | + | + | +/- | +/- | ↑ | Ν | ↑ | ↑ | N | See the table below for the details about types. | |||
Vessel wall disorders | Metabolic and Inflammatory Disorders |
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+ | + | +/- | - | - | N | ↑/N | N | N | N | - | |
Inherited Disorders of the Vessel Wall |
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+ | + | +/- | - | - | N | ↑/N | N | N | N | - | |||
Coagulation factor disorders | Fibrinogen deficiency | Different types of the fibrinogen disorders: |
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_ | + | + | +/- | + | N | ↑ | ↑ | ↑ | ↑ |
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Prothrombin deficiency |
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+ | + | + | + | + | N | N | ↑ | ↑ | ↑ | - | |||
Factor V deficiency |
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_ | + | + | + | + | N | ↑ | ↑ | ↑ | N | The severity of bleeding is only partly related to the degree of factor V deficiency. Some patients with undetectable plasma levels of factor V experience only relatively mild bleeding. | |||
Factor VII deficiency |
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+ | + | + | N | ↑ | N | N | Thrombosis occurs in inherited factor VII deficiency most cases are associated with the administration of factor VII replacement therapy | ||||||
Factor X deficiency |
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+ | + | + | + | + | N | N | ↑ | ↑ | N | - | |||
Factor XII deficiency |
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_ | _ | _ | _ | _ | N | N | N | ↑ | N | ||||
High molecular weight kininogen (HMWK) deficiency |
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_ | _ | _ | _ | _ | N | N | N | ↑ | N | ||||
Prekallikrein deficiency |
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_ | _ | _ | _ | _ | N | N | N | ↑ | N | ||||
Factor XIII deficiency | Types:
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-/+ | -/+ | -/+ | -/+ | -/+ | N | N/ | N/↑ | N | N |
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Hemophilia[6][7][8] | Type A deficiency |
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_ | _ | + | + | + | N | N | N | ↑ | N | - | ||
Type B deficiency |
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_ | _ | + | + | + | N | N | N | ↑ | N | - | |||
Type C deficiency |
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_ | _ | + | Rare | Rare | N | N | N | ↑ | N | - | |||
Rare diseases | Disseminated Intravascular Coagulation |
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+ | + | _ | + | + | ↓ | ↑ | ↑ | ↑ | N | - | ||
Vitamin K Deficiency |
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+ | + | + | + | + | N | ↑ | ↑ | Normal or mildly prolonged | N | - |
Type of VWD | Type of factor deficiency | Prevalence | Inheritance pattern | Clinical manifestations | VWF activity | RIPA | Factor VIII | |
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Type 1 | Quantitative/ partial | 60-70% | AD |
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↓ | ↓ | ↓ | |
Type 2 | 2A | Qualitative | 10% | AD/AR |
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↓ | ↓ | N or ↓ |
2B | Qualitative | 5% | AD |
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↓ | ↑ | N or↓ | |
2M | Qualitative | <1% | AD/AR |
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↓ | ↓ | N or ↓ | |
2N | Qualitative | <1% | AR |
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N | N | ↓ | |
Type 3 | Complete deficiency | 1-2% | AR |
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Absent | ↓ |
Low, 1-10% |
For more information on Von Willebrand disease click here
- ↑ Burns ER, Lawrence C (November 1989). "Bleeding time. A guide to its diagnostic and clinical utility". Arch. Pathol. Lab. Med. 113 (11): 1219–24. PMID 2535679.
- ↑ Gralnick HR, Rick ME, McKeown LP, Williams SB, Parker RI, Maisonneuve P, Jenneau C, Sultan Y (July 1986). "Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand's disease". Blood. 68 (1): 58–61. PMID 3487361.
- ↑ Mannucci PM, Lombardi R, Bader R, Vianello L, Federici AB, Solinas S, Mazzucconi MG, Mariani G (October 1985). "Heterogeneity of type I von Willebrand disease: evidence for a subgroup with an abnormal von Willebrand factor". Blood. 66 (4): 796–802. PMID 3876122.
- ↑ Kadir RA, Economides DL, Sabin CA, Owens D, Lee CA (February 1998). "Frequency of inherited bleeding disorders in women with menorrhagia". Lancet. 351 (9101): 485–9. doi:10.1016/S0140-6736(97)08248-2. PMID 9482440.
- ↑ Kouides PA, Byams VR, Philipp CS, Stein SF, Heit JA, Lukes AS, Skerrette NI, Dowling NF, Evatt BL, Miller CH, Owens S, Kulkarni R (April 2009). "Multisite management study of menorrhagia with abnormal laboratory haemostasis: a prospective crossover study of intranasal desmopressin and oral tranexamic acid". Br. J. Haematol. 145 (2): 212–20. doi:10.1111/j.1365-2141.2009.07610.x. PMID 19236375.
- ↑ Zimmerman B, Valentino LA (2013). "Hemophilia: in review". Pediatr Rev. 34 (7): 289–94, quiz 295. doi:10.1542/pir.34-7-289. PMID 23818083.
- ↑ Bolton-Maggs PH, Pasi KJ (2003). "Haemophilias A and B." Lancet. 361 (9371): 1801–9. doi:10.1016/S0140-6736(03)13405-8. PMID 12781551.
- ↑ Knoebl P, Marco P, Baudo F, Collins P, Huth-Kühne A, Nemes L; et al. (2012). "Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)". J Thromb Haemost. 10 (4): 622–31. doi:10.1111/j.1538-7836.2012.04654.x. PMID 22321904.