[Coagulation Problems] An Approach to Bleeding and Bruising, Part 1 From PedsCases

Links to and excerpts from PedsCases‘ podcast and script,  An Approach to Bleeding and Bruising, Part 1,
by Gabriel Blank Jan 14, 2021.

All that follows is from the above resource.

This podcast will highlight an approach to bleeding and bruising in pediatric patients and is part 1 of a 2 part series. It was developed by Gabriel Blank, a fourth-year medical student at the University of British Columbia, in collaboration with Dr. Tom McLaughlin, a general pediatrician at BC Children’s Hospital.

Related Content

How Bleeding Happens:

Let’s first go through a crash course on  hemostasis. There are two main processes that stop bleeding, formation of a platelet plug – primary hemostasis – and stabilization of this plug
through the coagulation cascade, or secondary hemostasis.

Primary hemostasis starts when platelets contact damaged blood vessels, releasing granules that promote platelet

In secondary hemostasis, the coagulation cascade turns fibrin monomers into a blood stopping fibrin polymer. Along with vessel constriction, the aggregated platelets and fibrin polymers work in unison to stop bleeding.1

Non-Hematologic Causes of Bleeding and Bruising:

Now onto the approach. The conditions that cause apparent bruising or bleeding can be broadly categorized as nonhematologic and hematologic. Non hematologic causes include dermatologic, vascular, accidental trauma and inflicted trauma (also known as child abuse).

Dermatologic findings can sometimes be mistaken for bruises or bleeding under the skin. Causes include hemangiomas, eczema, and congenital dermal melanocytosis. Congenital dermal melanocytosis is more colloquially referred to as Mongolian spots and is characterized by blue-gray patches commonly on the lower back and buttocks.2

Vascular type bleeding leads to cutaneous bleeds, or bleeding in the skin, and may progress to hemorrhaging into organ parenchyma. Causes include vasculitides, inherited connective tissue disorders, chronic steroid use and vitamin C deficiency.3

Vasculitis is a fancy way of saying blood vessel inflammation. The most common vasculitis in children is IgA vasculitis, also known as Henoch Schonlein Purpura (HSP). It is characterized by colicky abdominal pain, arthritis, and a raised reddish-purple rash, known as palpable purpura, typically over the buttocks and lower extremities.4

Ehlers-Danlos is the archetypal inherited connective tissue disorder. It presents with a history of poor wound healing, sprains, and joint dislocations with hypermobile joints and
paper-thin scars on exam.3,5

Alright we covered dermatologic mimics of cutaneous bleeding, such as hemangiomas, eczemaand congenital dermal melanocytosis, and four causes of vascular type bleeding: vasculitis, inherited connective tissue disorders, chronic steroid use, and vitamin C deficiency.

Accidental trauma encapsulates the non-pathologic, unintentional causes of bruises. Bruises are, in fact, very common in mobile children and increase with mobility.

While bruising is very common in all kids, it is also the most common sign of inflicted trauma (or physical child abuse). Inflicted injuries should be suspected when the severity or distribution of the injury does not align with the history, the history keeps changing, or the injury is inconsistent with the developmental age of the child.2 As we’ve said before on PedsCases, ifyou’re not cruising, you’re not bruising. In fact, less than 1% of non-independently mobile babies show any signs of bruising.6

If you suspect child abuse, Child Protective Services must be notified!

Hematologic Causes of Bruising and Bleeding:

Next up, hematologic causes of bruising and bleeding. Broadly, the two heme ingredients responsible for stopping bleeding are platelets and coagulation factors.1 The location of the
bleeding can be a clue to where the problem is.

If platelets are the issue you classically see cutaneous bleeding, immediate surgical bleeding, and bleeding from mucous membranes such as epistaxis, gum bleeding, and menorrhagia.

Cutaneous bleeding is usually characterized by petechiae, which are, non-blanchable discrete lesions that are less than 2-3 mm long. These petechiae can coalesce into larger lesions known as purpura, and even larger areas called ecchymoses.9,10

In contrast, coagulation cascade can cause deep, often palpable
ecchymosis, soft tissue hematomas, and hemarthroses, which is bleeding into the joint space.9,10

This episode focuses on coagulation cascade abnormalities. We will talk about platelet problems in the next podcast.

Coagulation Defects:

Let’s start with a rapid review of the coagulation cascade, with some quick mnemonics to hopefully make it less painful.

There are three pathways: intrinsic, extrinsic, and common. The
intrinsic and extrinsic pathways both converge on the common pathway.

For the common pathway, think of Canadian currency denominations. It starts at factor ten then goes factors five,
two, and one.

Extrinsic pathway involves factor VII, a lucky number, and what is luck but an extrinsic benefit. Factor VII, extrinsic pathway.

The intrinsic pathway is the other factors, starting
at 12—factors 12, 11, 9, and 8.

Now three main clotting tests are PT, aPTT, and mixing studies.1  PT is used to calculate INR, which is used to monitor the effect of the anticoagulant warfarin. PT measures the common and extrinsic pathways.

aPTT measures the common and intrinsic pathways.

If either PT or aPTT are abnormal, you can do a mixing
study, where you combine normal plasma with the patient’s plasma.

If the clotting time corrects think factor deficiency. If it does not correct then a factor inhibitor, typically an autoantibody, is present.1

There you have it, PT for extrinsic pathway, aPTT for intrinsic
pathway, and mixing studies for factor inhibitors.

Now onto coagulation defects. These can again be conceptually broken down into inherited and acquired causes.

The three most common inherited causes in order are von Willebrand Disease, Hemophilia A, and Hemophilia B.

Based on lab data, von Willebrand has a prevalence
of 1%, though the percent of people who require specialist care is closer to 0.01%.11 Its marked by a deficiency or abnormal function in von Willebrand factor, a molecule responsible for binding platelets to damaged vessel walls and stabilizing factor VIII. The disordered platelet function causes mucocutaneous bleeding, though because von Willebrand factor stabilizes factor VIII, severe cases may also have joint bleeding.11 For more talk on von Willebrand Disease, see the PedsCases episode dedicated to it.

Hemophilia A is caused by Factor VIII deficiency. . . . Hemophilia A occurs in 1 in 5000 live male births. Hemophilia B is caused by a deficiency in factor IX and is present in 1:20000 male births.2,12,13 3 Notice, I am emphasizing male births. This is because both Hemophilias are X-linked recessive, making them more common inmales. And since they affect factors VIII  and IX the intrinsic pathway, not extrinsic, is impaired. This classically gives a prolonged aPTT with a normal PT.8 Obvious signs of coagulation problems, such as easy bruising, intramuscular hematomas, and hemarthroses, usually do not
begin until the child starts to cruise.9 Before children start to cruise, diagnostic clues can be bleeding with circumcision, excessive bleeding with bloodwork, bleeding with forceps or
vacuum delivery, or serious spontaneous bleeding into the head or joints. There is a family history of hemophilia in about 2/3 of cases.

The cornerstone of effective hemophilia treatment is quick administration of factors. Factor VIII in hemophilia A, and factor IX in hemophilia B. Lowresource settings unable to afford factors commonly give FFP and cryoprecipitate.12, 13

Next up to bat, the acquired causes of coagulation problems. These can be from consumption of coagulation factors, or decreased production of factors. Consumption of coagulation factors could be due to the systemic inflammation in DIC or factor inhibitors.8 Factor inhibitors include anticoagulants like warfarin and autoantibodies.9 Antibodies against specific factors are much less common in children than in the elderly, though about one third of hemophilia patients receiving factor infusions can develop specific factor autoantibodies.9,14

Regarding decreased factor production, two main causes are liver disease and vitamin K deficiency.8,15

We have another episode dedicated to Vitamin K deficiency in newborns that you can listen to for a more thorough and well-structured explanation. In short, it can occur as soon as the first 24 hours after birth for the early onset variant, and up to 6 months for late onset. A big cause is low intake of vitamin K, with chronic malabsorption also being a major culprit behind late onsetbleeding. We prophylax against “hemorrhagic disease of the newborn” with vitamin K IM at birth.16

Alright, we discussed some inherited and acquired causes of coagulation cascade defects. Inherited causes include the hemophilias and von Willebrand disease. Acquired coagulation problems of note include DIC, factor inhibitors, liver disease and vitamin K deficiency

History and Physical Rapid Review:

With this information under our belt, let’s review the key components of the history andphysical exam.

First and foremost, you should ask about a history of previous bleeding problems, such as cephalohematoma at birth, petechiae at clothing line pressure sites, and post-circumcision, post-venipuncture, and umbilical stump bleeding.2 Make sure to elucidate the type of bleeding. Remember, this classically means deep bleeding for coagulation problems and mucocutaneous bleeding for platelet issues. Of course, you can ask questions for specific disorders. This
includes constitutional symptoms for malignancy, family history for inherited causes, and drug history for pharmacologic causes. The timeline of onset can also help differentiate more rapid onset bleeding causes from potentially more chronic pathology, like Hemophilia and other inherited causes

Conclusion and Review:

Let’s finish things off by reviewing what we learned. Causes of bleeding and bruising can be differentiated into non-hematologic and hematologic aetiologies. Non-hematologic causes include vascular pathology like IgA-Vasculitis, dermatologic mimickers like hemangiomas, and both accidental and inflicted trauma.

Think of inflicted trauma when you have large unexplained bruises away from bony prominences in a non-mobile child.

Coagulation cascade pathology can be categorized as inherited or acquired.

Inherited causes of coagulation abnormalities include the Hemophilias and von Willebrand disease.

Two categories of acquired coagulation problems are factor destruction, think DIC or factor inhibitors, and decreased
production, think liver disease or vitamin K deficiency.

On history you should ask questions that point toward a bleeding disorder, such as cephalohematoma at birth, umbilical stump bleeding, petechiae at clothing pressure sites, and post-circumcision or post-venipuncture bleeding.

Then, ask about the type of bleeding.

Classically, mucocutaneous suggests platelets pathology,
deep bleeds point to coagulation problems, and bleeding in the skin and organ parenchyma suggests vascular pathology.

On physical exam, carefully examine the skin, while also assessing for lymphadenopathy, hepatosplenomegaly, and skeletal malformations or injuries.


This entry was posted in Pediatric Hematology, PedsCases Podcasts. Bookmark the permalink.