AssessmentsMixed platelet and coagulation disorders: Pathology review
USMLE® Step 1 style questions USMLE
A 4-year-old girl presents to the emergency department with abdominal pain, diarrhea, and fatigue. The patient was in her usual state of health until yesterday afternoon, when her family returned home from a barbeque. The patient is otherwise healthy and takes no medications aside from amoxicillin for a recent episode of otitis media. According to her parents, the patient’s urine has looked “darker” than usual. Temperature is 39.0°C (102.2°F), pulse is 115/min, respirations are 22/min, and blood pressure is 100/70 mmHg. Physical examination demonstrates a pale appearing girl with diffuse abdominal tenderness to palpation, delayed capillary refill, and gingival bleeding. Multiple tiny, brownish-purple, blanchable spots are noted under the skin. Which of the following laboratory findings are most consistent with this patient’s disease process?
Contributors:Sam Gillespie, BSc, Maria Emfietzoglou, Robyn Hughes, MScBMC, Samantha McBundy, MFA, CMI
At the emergency department, a 70 year old male named Max is admitted because of high fever with chills, and hypotension.
He complains of having urinary urgency, frequency and dysuria, or painful urination, for the last few days.
A few hours after admission, he rapidly deteriorates and starts to bleed from venipuncture sites. Urine and blood cultures are ordered and are both positive for gram negative rods.
Lab tests show low platelet count, and bleeding time, PT and PTT are prolonged, fibrinogen is decreased and d-dimers are elevated. Peripheral blood smear shows schistocytes.
Now, there’s also an 18 year old female, named Sylvia, that came in with recurrent severe nose bleeds. She also complains of heavy menstrual periods.
Family history reveals her father also suffered from bleeding diathesis. Lab tests show normal platelet count, prolonged bleeding time and PTT, and normal PT.
Both Max and Sylvia are suffering from a hemostasis disorder. Hemostasis disorders, also known as bleeding disorders, can be broadly divided into three groups.
The first includes problems with primary hemostasis, which is the formation of the weak platelet plug, and so, they’re referred to as platelet disorders.
Now, the second group includes problems with secondary hemostasis, which is making a strong fibrin clot through activation of the intrinsic, extrinsic and common coagulation pathways, and are also known as coagulation disorders.
And the last group includes disorders that affect both primary and secondary hemostasis and are known as mixed platelet and coagulation disorders.
For your exams, it’s important to know that DIC can occur in response to serious conditions including gram negative bacterial sepsis, trauma, and obstetric complications such as abruptio placenta and retained dead fetus in utero, acute pancreatitis, malignancies such as adenocarcinomas and promyelocytic leukemia, nephrotic syndrome, snakebites, and transfusion reactions.
Okay, whatever the cause, there is a release of a procoagulant that tips the scales in favor of clot formation.
Procoagulants could be enzymes that help to proteolytically cleave and activate clotting factors or proteins like bacterial components such as lipopolysaccharide or tissue factor also known as thromboplastin.
For your test, remember that the release of tissue factor from abruptio placenta into the maternal circulation, is, in fact, the most common cause of DIC in pregnancy.
DIC leads to widespread clotting, which can block off small arteries leading to organ ischemia.
These clots also act like jagged rocks in a river and damage the red blood cells floating by, causing microangiopathic hemolytic anemia.
These damaged RBCs can be seen on a blood smear as schistocytes but sometimes they get destroyed completely.
At the same time, excessive clot formation depletes platelets and clotting factors, which paradoxically, leads to increased bleeding.
Now, let’s move onto von Willebrand disease, the most common inherited bleeding disorder. It’s usually caused by autosomal dominant mutations of von Willebrand factor.
These proteins normally serves as the glue between the platelet receptor Gp1b and the collagen underneath the endothelial cells.
So, for the test remember that if there’s a problem with von Willebrand factor, it’s hard for platelets to adhere to collagen in damaged blood vessels, leading to impaired platelet function.
Inherited von Willebrand disease is subclassified into type 1, which is a decrease in the quantity of von Willebrand factor, and type 2, which is a decrease in the function of von Willebrand factor.
Meanwhile, von Willebrand factor also stabilize factor 8 of the intrinsic coagulation pathway.
So without von Willebrand factor, there’s less functioning factor 8 around, leading to decreased activation of the coagulation cascade.
Alright, so mixed platelet and coagulation disorders affect both primary and secondary hemostasis, and as a result they can present with symptoms caused by dysfunctions in both pathways.
Primary hemostatic, or platelet, problems usually present with petechiae, which are pinpoint superficial skin bleeds, anterior epistaxis, which are usually mild nosebleeds, immediate bleeding after surgical procedures, like tooth extraction, or bleeding from mucosal surfaces, like gingival, gastrointestinal, or vaginal bleeding.
In contrast, secondary hemostatic, or coagulation, problems can present with large bruises after minor trauma, like bumping into a door.
They also suffer from ecchymoses, which is discoloration caused by bleeding under the skin, deep tissue hematomas, hemarthrosis, which is bleeding inside the joint space, posterior epistaxis, which causes a severe nosebleed, GI bleeding, urinary bleeding, and persistent bleeding after surgical procedures.
- "Robbins Basic Pathology" Elsevier (2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
- "Diagnosis and Treatment of Benign Bleeding Disorders" Journal of the Advanced Practitioner in Oncology (2016)
- "Bleeding and Coagulopathies in Critical Care" New England Journal of Medicine (2014)
- "Disseminated intravascular coagulation" Nature Reviews Disease Primers (2016)
- "von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA)" Haemophilia (2008)
- "The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology" British Journal of Haematology (2014)