Pales DSAs Flashcards
Type I VWD
partial quantitative deficiency
3/4 of pts with VWD
variable bleeding severity (mild to severe)
AD inheritance
VWF activity and RIPA decreased
RIPA may be normal in mild disease
Multimer electrophoresis: All multimers present and uniformly decreased
Tyype 2A VWD
qualitative variant
moderate to severe bleeding
AD or AR inheritance
VWF activity and RIPA decreased
Factor VIII levels may be normal or reduced
Multimer electrophoresis: Decreased large multimers
Type 2B VWD
Moderate to severe bleeding
Thrombocytopenia or giant platelets may be seen
AD inheritance
VWF activity decreased
RIPA increased
Factor VIII levels may be normal or reduced
Thrombocytopenia/giant platelets
Multimer electrophoresis: Decreased large multimers
DDAVP may be used to treat minor bleeding if a trial of DDAVP performed when the patient is not bleeding
Type 2M VWD
rare
Moderate to severe bleeding
AD or AR inheritance
VWF activity and RIPA decreased
Factor VIII levels may be normal or decreased
Multimer electrophoresis: All multimers present and uniformly decreased
Type 2N VWD
Rare
Clinically similar to hemophilia A with joint, soft tissue, urinary bleeding
AR inheritance
VWF activity and RIPA normal
Factor VIII levels low (5 to 15%)
Multimer electrophoresis: Normal
Type 3 VWD
severe extremely rare Clinically similar to hemophilia A with joint and soft tissue bleeding Severe mucosal bleeding AR inheritance
VWF activity and RIPA absent or markedly decreased
Factor VIII levels low (1 to 10%)
Multimer electrophoresis: Undetectable or too faint to visualize
do not use DDAVP
When to suspect von Willebrand disease
— Patients with von Willebrand disease (VWD) can become symptomatic at any age. The patient’s personal and family history of bleeding episodes is important, and one needs to specifically seek a history of challenges such as invasive dental procedures, tonsillectomy, other surgical procedures (particularly involving mucous membrane surfaces), and menstrual and peripartum bleeding. The use of a bleeding assessment tool is recommended.
typical history: lifelong easy bruising, epistaxis > 10 minutes, excessive menstrual bleeding
In patients with type 2N VWD, the bleeding is due to low factor VIII levels and mimics the findings seen in classical hemophilia, including soft tissue, joint, and urinary bleeding, and bleeding after invasive procedures
In patients with type 3 VWD, both types of bleeding (ie, mucocutaneous and soft tissue bleeding as well as joint bleeding) may occur (see ‘Type 3’above
Initial testing for VWD
Plasma von Willebrand factor (VWF) antigen (VWF:Ag)
●Plasma VWF activity (ristocetin cofactor activity, VWF:RCo and VWF collagen binding VWF:CB)
●Factor VIII activity (FVIII)
If there is still a high index of suspicion for VWD in the face of normal initial results
further testing is carried out which first includes repeating the initial tests. If the repeat VWF levels are normal, other causes of bleeding should be investigated. If one of the VWF tests is abnormal, the following specialized assays should be performed to determine the type of VWD (table 2):
●VWF multimer distribution using gel electrophoresis
●Ristocetin-induced platelet aggregation (RIPA)
BLEEDING DIATHESIS
Bleeding that is spontaneous, excessive, or delayed in onset following tissue injury results from one or more of the following:
•A localized pathologic process
•Disorders involving vascular integrity
•Disorders of platelet number and/or function
•Disorders of the various coagulation factors
•Increased fibrinolysis
when bleeding diathesis diagsnosis is not immediately apparent, 3 tests:
: platelet count, prothrombin time (PT), and activated partial thromboplastin time (aPTT)
THROMBOCYTOPENIA
ie, platelet count under 150,000/microL may be associated with a variety of conditions, with associated risks that range from life-threatening to none. We are most concerned about spontaneous bleeding with counts under 10,000/microL, and surgical bleeding with counts under 50,000/microL. Rarely, thrombocytopenia is associated with a risk of thrombosis rather than bleeding.
certain causes of thrombocytopenia that are medical emergencies
suspected heparin-induced thrombocytopenia [HIT], thrombotic thrombocytopenic purpura [TTP], hemolytic uremic syndrome [HUS], drug-induced thrombotic microangiopathy [DITMA], or bone marrow failure syndrome with severe pancytopenia
In asymptomatic outpatients with thrombocytopenia, common diagnoses include
immune thrombocytopenia (ITP), occult liver disease, HIV infection, and myelodysplastic syndromes. Congenital thrombocytopenias (sometimes misdiagnosed as ITP) may also occur
We confirm thrombocytopenia by
repeating the CBC and reviewing the peripheral blood smear; obtain prior platelet counts, if available, and assess other hematologic abnormalities. The pace of the subsequent evaluation, further testing, and hematologist consultation depends on the clinical presentation, which can range from asymptomatic to acutely ill.
Thrombocytopenia history should focus on
prior platelet counts, family history, bleeding, medications, over-the-counter remedies, infectious exposures, dietary practices, and other medical conditions (eg, hematologic disorders, rheumatologic conditions, surgery, transfusion). The physical examination should evaluate bleeding, lymphadenopathy, hepatosplenomegaly, thrombosis, and organ involvement.
Management of patients with thrombocytopenia
depends on the underlying diagnosis. General principles that apply to all patients include avoidance of medications that interfere with platelet function unless alternatives are unavailable; coordination with anesthesiologists and surgeons before invasive procedures, and correction of coagulation abnormalities. Activity restrictions are often not needed.
Common causes of disseminated intravascular coagulation (DIC)
include sepsis, malignancy, and trauma, as well as obstetrical complications and hemolysis from acute hemolytic transfusion reaction. Additional causes are seen less often but may be considered if none of the above conditions are obviously present.
A variety of initiating procoagulants may contribute to DIC
including tissue factor (TF), bacterial products, microparticles, and cell-free DNA (cfDNA) and DNA binding proteins from neutrophil extracellular traps (NETs).
Acute DIC generally is seen
in patients with a history of sepsis, malignancy (especially acute promyelocytic leukemia), or ABO-incompatible blood transfusion. Clinical findings include bleeding; thrombocytopenia; prolonged PT and aPTT; low plasma fibrinogen; elevated plasma D-dimer; and microangiopathic changes on peripheral blood smear, although none of these are highly specific.
•Chronic DIC
generally is seen in patients with a history of malignancy, especially pancreatic, gastric, ovarian, or brain tumors; venous or arterial thromboembolism; mild or no thrombocytopenia; normal or mildly prolonged PT and aPTT; normal or slightly elevated plasma fibrinogen; and elevated plasma D-dimer.
management of DIC
For patients who are not bleeding, we do not routinely use prophylactic transfusion of platelets and coagulation factors, as long as the platelet count is ≥10,000/microL. One international consensus group suggested using a platelet count threshold of 20,000/microL in the absence of bleeding. However, treatment is justified in patients who have serious bleeding, are at high risk for bleeding, or require invasive procedures. Platelets and/orplasma products should not be withheld in these settings for fear of “fueling the fire.” In contrast, the administration of antifibrinolytic agents, such as tranexamic acid (TXA), epsilon-aminocaproic acid (EACA), or aprotinin, is generally contraindicated.
anticoagulation in DIC
There is little evidence to support the use of anticoagulation in patients with acute or chronic DIC, with the exceptions of prophylaxis during the perioperative period or a hospital admission for an acute medical illness, and treatment of venous or arterial thromboembolism. Patients with purpura fulminans appear to benefit from the administration of protein C concentrate
improvement in DIC
Laboratory abnormalities associated with DIC usually begin to improve within a few days after the inciting trigger is removed or terminated. Resolution of these abnormalities may take longer if significant liver damage is present.
HEMOPHILIA
Hemophilia A (factor VIII [factor 8] deficiency) and hemophilia B (factor IX [factor 9] deficiency) are inherited bleeding disorders with X-linked recessive transmission. Severity depends largely on the factor activity level, with severe disease defined as under 1 percent of normal; moderate disease as 1 to 5 percent, and mild disease as >5 percent.
Patients with severe hemophilia experience
spontaneous bleeding and bleeding in response to minor trauma that is out of proportion to the degree of injury, which can begin as early as birth. Delayed bleeding after trauma is common; it can be massive or may persist as continuous oozing for days or weeks. In contrast, mild hemophilia may only become apparent when there is a significant hemostatic challenge such as trauma or surgery.
Most infants with severe hemophilia present within the first year to one and a half years of life with easy bruising, hemarthrosis, bleeding due to oral injury, or after an invasive procedure.
•Life-threatening bleeding can occur at delivery, with trauma, or spontaneously. Approximately 3 to 5 percent of infants with severe hemophilia develop subgaleal or intracerebral hemorrhage in the perinatal period.
Hemophilia common sites of bleeding
include intracranial hemorrhage (ICH), joints and soft tissues, and oral mucosa. ICH is relatively rare compared with other sites, but it is one of the most dangerous and life-threatening events. Hemarthrosis (ie, hemorrhage into a joint) is the most common site for bleeding in ambulatory patients.
Late complications from hemophilia bleeding
include neurologic sequelae of intracranial hemorrhage, and joint destruction from repetitive hemarthroses (ie, hemophilic arthropathy). Complications of factor infusion include the potential for infection, which has declined dramatically since the mid 1980s and is extremely low, and development of inhibitory antibodies to the infused factor.
Female carriers of hemophilia are
heterozygous for the genetic defect (ie, they have one normal allele and one abnormal allele) and are expected to have approximately 50 percent of normal factor production, which is generally sufficient to prevent clinical bleeding. However, some hemophilia carriers have symptoms similar to males with mild hemophilia. Potential hemophilia carriers should be tested using genetic testing. If carrier status is confirmed, measurement of factor levels is appropriate to guide management during hemostatic challenges.
hemophilia diagnostic evaluattion
begins with a thorough review of the patient’s personal bleeding history and family history; however, approximately one-third of patients with hemophilia have a negative family history, typically due to a de novo mutation. Laboratory testing includes screening tests of hemostasis, factor activity levels, and/or genetic testing (also called molecular testing).
Diagnostic criteria for hemophilia
include confirmation of a factor activity level below 40 percent of normal (below 0.40 international units [IU]/mL), or a hemophilia gene mutation. A normal von Willebrand factor antigen (VWF:Ag) should also be documented in patients with reduced factor VIII activity levels, to eliminate of the possibility of von Willebrand disease (VWD).
hemophilia Carrier females who become pregnant should
undergo evaluation of fetal sex using a non-invasive method, such as ultrasound, because only male children are potentially affected. Maternal factor levels should be determined prior to invasive procedures including neuraxial anesthesia. The maternal and fetal risks of vaginal versus Cesarean delivery should be discussed. Generally, confirmatory testing to diagnose or exclude hemophilia in a male child is performed at birth, on cord blood. Circumcision should be deferred until the diagnosis is confirmed or excluded.
The differential diagnosis of hemophilia includes
other inherited bleeding disorders (eg, VWD, platelet disorders, other factor deficiencies) and acquired coagulation factor inhibitors.
