Bleeding Disorders
Definition: Abnormal bleeding results from disorders of initiation of hemostasis and consolidation of hemostasis. Initiation of hemostasis involves the vascular endothelium and platelets. This manifests as purpura and hemorrhage from or into skin and mucous membranes. Consolidation of hemostatis involves the coagulation and fibrinolytic pathways. This manifests clinically as uncontrolled hemorrhages from or into deeper tissues.
Purpura: bleeding disorders result from abnormalities of the endothelium (vascular purpura), abnormalities of platelet function, or thrombocytopenia
Vascular purpura: damage of vascular endothelium is a common cause of purpura. Infection are important, causing hemorrhage through either direct toxicity to the endothelium or immune damage. Seen in HIV patients also.
Defective platelet function: Purpura from this cause can be seen in hemorrhagic fevers (lassa, dengue), alcoholism, hepatic cirrhosis, uremia, and leukemias. It can also result from ingestion of drugs such as NSAIDs.
Thrombocytopenia: an abnormally low platelet count may result from defective production, increased destruction or splenic pooling. This is can present with splenomegaly and anemia.
Clinical presentation of bleeding disorders:
Platelet: site: skin and mucous membranes, lesions: petechiae and ecchymoses, bleeding: after minor cuts and mild bleeding after surgery
Coagulation defects: site: deep in soft tissue (muscle, joints), lesions: hemarthroses and hematomas, bleeding: unusual after minor cuts but can be severe after surgery\
Types of Bleeding Disorders
Platelet Disorders
Thrombocytopenia and risk of bleeding:
-platelet count > 100,000: no risk of bleeding
-platelet count 50,000-100,000: risk with major trauma
-platelet count 20,000-50,000: risk with minor trauma
-platelet count < 20,000: risk of spontaneous bleeding
Etiologies:
Decreased Production of platelets:\
-infections like typhoid, brucellosis
-hypocellular bone marrow: seen in aplastic anemia, drugs (thiazides, antibiotics) and alcohol
-cellular bone marrow: seen in leukemia
-marrow replacement: seen in hematologic and solid tumors, granulomas (TB)
Increased Destruction of platelets:
-immune mediated:
-Primary: immune thrombocytopenic purpura (ITP)
-treatment: steroids, do not give platelets
-Primary: onyalai. A profound acquired thrombocytopenia that affects young people in southern africa. Clinical features: hemorrhagic bullae on mucous membranes and epistaxis. Treatment: transfusions and possible splenectomy
-Secondary: infection (HIV, malaria, dengue), lymphoproliferative disorders (lymphoma), drugs (heparin, quinine, sulfonamides), autoimmune disease
-non immune mediated:
-DIC (disseminated intravascular coagulation) is the widespread or uncontrolled deposition of fibrin in the circulation, followed by increased activation of fibrinolysis. Clinical features: hemorrhage, depleted platelets, decreased fibrogen and increased PT/PTT, microangiopathic hemolytic anemia with schistocytes on blood smear. Presents with an underlying condition (pregnancy, infection) and can range from abnormal lab values, minor bleeding or extreme hemorrhage. Treatment: treat underlying condition, for severe hemorrhage, give cryoprecipitate, platelets, FFP to restore missing coagulation factors.
-HUS/TTP: HUS (hemolytic uremic syndrome: microangiopathic hemolytic anemia + thrombocytopenia + renal failure) TTP (thrombotic thrombocytopenic purpura: microangiopathic hemolytic anemia + thrombocytopenia + alerted mental status + fever + renal failure
-vasculitis, pre-eclampsia/HELLP syndrome
-abnormal pooling of platelets: seen in splenic sequestration
Coagulopathies:
These occur in 2 forms: congenital (hemophila A, hemophilia B, and von Willebrand’ disease. 2nd form is acquired (malabsorption, liver disease, DIC)
Congenital coagulopathy:
-Types: 1) hemophilia A = factor VIII deficiency 2) hemophilia B = factor IX deficiency 3) von Willebrand’s disease: deficiency in von Willebrand’s factors
-Clinical features: bleeding into joints and muscles is common
-Diagnosis: by history, family history, increased PTT and factor VIII assay
-Management: hemophila A patients should avoid NSAIDs, major bleeding requires factor VIII or cyroprepitate. Hemophilia B patients are best treated with factor IX. Von Willebrand’s disease is best management with cryoprecipitate or desmopressin
Acquired coagulopathy:
-Vitamin K deficiency or Malabsorption:
-etiology: malnutrition, decreased absorption, liver disease (decreased stores)
-diagnosis: prolonged PT which becomes normal with administration of vitamin K 10 mg IV
-Liver disease: bleeding cause is multifactorial including coagulation factor deficiency, liver no longer producing adequate amounts of fibrinogen, impairment in synthesis of vitamin K dependent factors
-bleeding with liver disease should be treated with cryoprecipitate, FFP
General evaluation for bleeding disorders:
-Take a good history and physical exam asking about bleeding tendencies, where they bleed and when, family history, gum bleeding, heavy menstrual periods and excessive bleeding after cuts. Examine the skin and joints carefully looking for purpura, examine for splenomegaly
-obtain FBP, PT/PTT and look at blood smear
-obtain reticulocyte count
-treatment is based on underlying cause of bleeding disorder
Bleeding disorders Clinical Cases
Case 1
40 year old male with history of HIV (CD4 count 300) comes to the hospital with complaints of a new rash. He tells you that he started noticing it a few months ago. There is no pain associated with the rash and he only noticed it on his lower extremities. He denies fevers, nightsweats, shortness of breath or cough. He has been taking anti-retrovirals for 1 year now and has not had any problems.
On exam, his blood pressure is 106/80 and heart rate is 70. He is afebrile.
Gen: slightly wasted appearing
HEENT: anicteric sclera
Pulm: clear to auscultation bilaterally
CV: regular rate and rhythm with no murmurs
Abd: soft nondistended
Ext: fine petechiae involving both of his lower extremities, nonblanching
1. What are petechiae caused by?
2. What do you think the cause of his petechiae is most likely related to?
3. Do you want to order any lab tests or images to further investigate?
4. If you saw schistocytes on the blood smear, what would your differential diagnosis include?
Answers:
- Petechiae are caused by disorders in platelet function.
- His petechiae are likely caused by thrombocytopenia secondary to HIV.
- Check a FBP, repeat CD4.
- Schistocytes would suggest a hemolytic process & peripheral destruction of platelets. E.g. TTP/HUS or DIC
