Bleeding diathesis

Jump to navigation Jump to search


Bleeding diathesis main page

Overview

Classification

Differential Diagnosis

Platelet disorders
Immune Thrombocytopenic Purpura
Thrombotic Thrombocytopenic Purpura
Hemolytic Uremic Syndrome
Thrombocytosis
Von Willebrand Disease
Coagulation disorders
Fibrinogen deficiency
Prothrombin deficiency
Factor V deficiency
Factor VII deficiency
Factor VIII deficiency
Factor IX deficiency
Factor X deficiency
Factor XI deficiency
Factor XII deficiency
High-molecular-weight kininogen deficiency
Prekallikrein deficiency
Factor XIII deficiency
Hemophilia
Rare diseases
Disseminated Intravascular Coagulation
Vitamin K Deficiency

Different types of Von-Willebrand diseases

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

Coagulation cascade

Antithrombotic control

Fibrinolysis

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:

  1. Thrombocytopenia: platelet count less than 150,000 per mm3
  2. Thromobcytosis: platelet countcmore than 450,000 per mm3
  3. Qualitative Disorders of Platelet function such as Von Willebrand Disease, inherited or acquired functional disorders.

Coagulation disorders

  1. 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.
  2. Coagulation factor disorders:
  3. Disseminated Intravascular Coagulation
  4. Vitamin K Deficiency
  5. Coagulation Disorders Associated with Liver Failure
  6. Acquired Inhibitors of Coagulation Factors

Differential Diagnosis

Differential diagnosis of "Bleeding disorders":
Category Sub-category Diseases History Clinical manifestation Laboratory testing Comments
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
  • History of prior infection
+ + + + + N N N
Medications-Induced thrombocytopenia + + + + + N N N
Heparin-Induced thrombocytopenia + + + + + N N
Immune Thrombocytopenic Purpura (ITP) + + + + + N N N
Inherited Thrombocytopenia
  • Family history
+ + + + + N N N
Thrombotic Thrombocytopenic Purpura (TTP) History of: + + + + + N N N
Hemolytic Uremic Syndrome History of:
  • Infections
+ + + + + N N N
Thromobcytosis + + Normal or slightly prolonged ɴ ɴ N
Qualitative Disorders of Platelet Function Inherited Disorders of Platelet Function Glanzmann’s thrombasthenia
  • Positive family history
+ + + - Rare N/↓ ɴ ɴ N
  • AR inheritance
  • Absence of the platelet Gp IIb/IIIa receptor/
  • Diminished for GP 2B-3A on flow cytometry
Bernard-Soulier syndrome
  • Positive family history
+ + + - - N/↓ N N N
  • AR inheritance
  • Absence of the platelet Gp Ib-IX-V receptor
  • On PBS: giant platelets
  • Ristocetin - no aggregation
Platelet storage pool disorder (SPD):
  • Positive family history
N
  • AD inheritance
  • Abnormalities of platelet granule formation
Acquired Disorders of Platelet Function + + + + + N
Von Willebrand Disease + + + + + Ν N
Vessel wall disorders Metabolic and Inflammatory Disorders
  • History of the underlying disease.
+ + +/- - - N
Inherited Disorders of the Vessel Wall
  • Positive family history
+ + +/- - - N
Coagulation factor disorders Fibrinogen deficiency _ + + + N The severity of bleeding in patients with fibrinogen disorders can be mild or severe, with higher bleeding risk in those with afibrinogenemia or lower levels of functional fibrinogen. The age of onset is also variable, with earlier onset in those with more severe deficiency.
Prothrombin deficiency + + + + + N N
Factor V deficiency _ + + + + 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 + + + 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
  • Prolonged bleeding following circumcision
+ + + + + N N N
Factor XII deficiency
  • Majority,asymptomatic
  • Recurrent miscarriages
  • Painful leg ulcers
_ _ _ _ _ N N N
HK deficiency
Prekallikrein deficiency
Factor XIII deficiency
Hemophilia Type A deficiency
  • Eeasy bruising
  • Inadequate clotting in trauma or mild injury
  • Spontaneous hemorrhage.
  • Hemarthrosis
  • Epistaxis
  • Gingival bleeding
_ _ + + + Unaffected Unaffected Unaffected Prolonged N
Type B deficiency
  • Neonatal bleeding
  • Trauma-related soft-tissue hemorrhage
  • Hemarthrosis
  • Hematomas
_ _ + + + Unaffected N N N
Type C deficiency
  • Family history
  • Bleeding after surgery or injury
_ _ + Rare Rare N N N N
Rare diseases Disseminated Intravascular Coagulation
  • Trauma
  • Burn
  • Crush injury
  • Sepsis
  • Malignancy
  • Obstetric complication: abruption, amniotic fluid embolism
  • Hemolytic anemia
+ + _ + + N
Vitamin K Deficiency
  • Bleeding after trauma
  • Epistaxis
  • Hematoma
  • Gastrointestinal bleeding,
  • Menorrhagia
  • Hematuria
  • Gum bleeding
  • Oozing from venipuncture sites
  • Easy bruisability
+ + + + + N Normal or mildly prolonged N
Coagulation Disorders Associated with Liver Failure
Acquired Inhibitors of Coagulation Factors
Different types of Von willebrand diseases can be differentiate from each other based on below table:
Type of VWD Type of factor deficiency Prevalence Inheritance pattern Clinical manifestations VWF activity RIPA Factor VIII Plt levels
Type 1 Quantitative/ partial
Type 2 2A
2B
2M
2N
Type 3
  1. Huizing M, Anikster Y, Fitzpatrick DL; et al. (2001). "Hermansky-Pudlak syndrome type 3 in Ashkenazi Jews and other non-Puerto Rican patients with hypopigmentation and platelet storage-pool deficiency". Am. J. Hum. Genet. 69 (5): 1022–32. doi:10.1086/324168. PMC 1274349. PMID 11590544. Unknown parameter |month= ignored (help)
  2. Novak EK, McGarry MP, Swank RT (1985). "Correction of symptoms of platelet storage pool deficiency in animal models for Chediak-Higashi syndrome and Hermansky-Pudlak syndrome". Blood. 66 (5): 1196–201. PMID 3902123. Unknown parameter |month= ignored (help)
  3. Hayward CP, Weiss HJ, Lages B; et al. (2001). "The storage defects in grey platelet syndrome and alphadelta-storage pool deficiency affect alpha-granule factor V and multimerin storage without altering their proteolytic processing". Br. J. Haematol. 113 (4): 871–7. PMID 11442477. Unknown parameter |month= ignored (help)